
Book. i^ 

Copyright N° ._ 



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THE ESTIYO- AUTUMNAL 

{REMITTENT) 

MALARIAL FEVERS 



CHARLES F, CRAIG, M.D. (Yale) 

Acting Assistant Surgeon U. S. Army ; Pathologist and Bacteriologist to the TJ. S. Army 

General Hospital, Presidio of San Francisco, Cal. ; Late Director of the Bacteriological 

Laboratories of the Sternberg U. S. A. General Hospital, Chickamauga Park, Ga., 

The Josiah Simpson U. S. A. General Hospital, Fortress Monroe, Va., 

and the Camp Columbia U. S. A. Hospital, Havana, Cuba ; 

Member of the American Medical Association, the 

American Microscopical Society, etc. . 



3IIugtrateti &e 3H»o Coloreti ©Iates anD ^tocntg^one Clinical €patta 



NEW YORK 
WILLIAM WOOD & COMPANY 

MDCCCCI 



p 



kf*\# 






THE LIBRARY OF 
CONGRESS, 

Two Cofitd Received 

AUG. 29 1901 

COPVRIGHT ENTRY 

CLASS CLxXc No. 
COPY B. 



Copyright by 

WILLIAM WOOD & COMPANY 

1901 



6@ount ©kaaant ©rinterg 
J. Horace McFarland Company 
Harrisburg • Pennsylvania 



Co 

GEORGE M. STERNBERG, M.D.,LL.D. 

SURGEON - GENERAL OF THE UNITED STATES ARMY 

<TO0 Volume te SDelsicated 

IN RECOGNITION OP HIS MANY GREAT AND 
VALUABLE DISCOVERIES IN BACTERIOLOGY AND 
SANITARY SCIENCE, AND AS A TOKEN OF THE 
REGARD AND ESTEEM OF THE AUTHOR 



PREFACE 

The reason for the preparation of this volume is given in 
the introduction. It deals with a much -neglected subject in the 
text -books upon medicine, and one which is of the utmost im- 
portance to the profession. It will be noticed that I have not 
considered the subject of hemoglobinuric fever at all. This is 
not an oversight on my part, but because I believe that in a 
work such as this the subject should be confined as much as 
possible. As the etiology of hemoglobinuric fever is still some- 
what in doubt, and as there are many excellent treatises upon 
it, I have thought it best to ignore it entirely. 

My gratitude is due the Surgeon -General of the Army for 
the opportunities afforded me to study the malarial fevers. To 
Colonel A. A. Woodhull, Assistant Surgeon -General of the 
Army, Colonel William C. Forwood, Assistant Surgeon -General, 
United States Arnry, and to Major Charles Richard, Surgeon, 
United States Army, my thanks are due for encouragement and 
assistance. 

I desire to take this opportunity of expressing my appre- 
ciation of, and thankfulness for, the uniform support and en- 
thusiasm of Lieutenant -Colonel A. C. Girard, Deputy Surgeon- 
General of the United States Army, in the scientific study of 
disease, and the methods of making such study available. With- 
out such cooperation much of this volume could not have been 
prepared. 

I have freely consulted the works of other investigators, and 
am particularly indebted to Marchiafava and Bignami, Thayer 
and Hewitson and Manson, for many valuable data and refer- 
ences. I have tried invariably to give credit where it is due. 

To my assistant, Dr. Jobling, I am indebted for the prepa- 
ration of the index. It is the earnest hope of the author that 

(v) 



VI PREFACE 

the studies contained in this volume may be of value to the 
medical profession and assist in the elucidation of the fevers of 
tropical and subtropical countries. The constant aim of the 
author has been to present as simply and accurately as pos- 
sible the facts connected with the fevers of malarial origin, 
known as estivo- autumnal, and I would urge upon the profes- 
sion the importance of thorough study of these fevers which are 
so prevalent and fatal in the tropics. 

CHARLES F. CRAIG. 

February 15, 1901. 



CONTENTS 



PAGE 

Introduction 1 

CHAPTER I 
Definition of Remittent Malarial Fever— Historical— General Remarks . 3 

CHAPTER II 

Description of the Parasites Causing the Remittent or Estivo- autumnal 
Malarial Fevers— The Quotidian Estivo -autumnal Parasite — The Ma- 
lignant Tertian Estivo-autumnal Parasite 15 

CHAPTER III 

The Crescentic, Ovoid and Flagellated Forms of the Estivo-autumnal 

Parasites . 24 

CHAPTER IV 
The Life-Cycle of the Estivo-autumnal Parasites within the Mosquito . 35 

CHAPTER V 
Cultivation and Inoculation Experiments — Phagocytosis — Classification . 40 

CHAPTER VI 

Examination of the Blood — Methods of Staining — The Structure of the 

Estivo-autumnal Parasites as Revealed by Staining 48 

CHAPTER VII 
Etiology — Predisposing Causes, General and Local 58 



CHAPTER VIII 

Etiology (continued) — Direct Infection — By Air — By Water— By Inocu- 
lation 62 

CHAPTER IX 

Transmission by Inoculation, from Man to Man — Incubation — Immunity 

—Spontaneous Recovery 71 

(vii) 



Vlll CONTENTS 

CHAPTEE X 

General Pathology of the Estivo-autunmal Malarial Fevers — Changes in 
the Red Corpuscles — Melanemia — Anemia — The Urine — The Etiology 
of the Fever k 79 

CHAPTER XI 
Special Pathology of the Estivo- autumnal Fevers — Acute Infections . . . 91 

CHAPTER XII 

Clinical Description of the Estivo -autumnal Malarial Fevers — Classifi- 
cation and Symptomatology of the Tertian and Quotidian Forms — 
Analysis of Symptoms and Physical Examination — Examination of the 
Blood 104 

CHAPTER XIII 

Clinical Illustrations of the Quotidian and Tertian Forms of the Estivo- 

autumnal Malarial Fevers 120 

CHAPTER XIV 
The Pernicious Forms of the Estivo -autumnal Malarial Fevers ...... 147 

CHAPTER XV 

Latent and Masked Estivo -autumnal Malarial Fevers — Subcontinued or ' 
Remittent Estivo -autumnal Malarial Fevers — Combined Infections . 159 

CHAPTER XVI 

Complications and Sequelae of the Estivo- autumnal Malarial Fevers . . 168 

CHAPTER XVII 
The Diagnosis and Prognosis of the Estivo -autumnal Malarial Fevers . 185 

CHAPTER XVIII 
The Prophylaxis and Treatment of the Estivo -autumnal Malarial Fevers. 199 



LIST OF PLATES AND CHARTS 

PAGE 

Plate I. The Quotidian and Tertian Estivo- autumnal Parasites . Facing 30 

Plate II. Stained Estivo - autumnal Parasites Facing 56 

Chart No. 1. Tertian Estivo-autumnal Malarial Fever 109 

Chart No. 2. Tertian Estivo-autumnal Malarial Fever 110 

Chart No. 3. Tertian Estivo-autumnal Malarial Fever 113 

Chart No. 4. Tertian Estivo-autumnal Malarial Fever 114 

Chart No. 5. Quotidian Estivo-autumnal Malarial Fever ....... 117 

Chart No. 6. Quotidian Estivo-autumnal Malarial Fever . 123 

Chart No. 7. Quotidian Estivo-autumnal Malarial Fever ....... 124 

Chart No. 8. Quotidian Estivo-autumnal Malarial Fever 127 

Chart No. 9. Quotidian Estivo-autumnal Malarial Fever 128 

Chart No. 10. Quotidian Estivo-autumnal Malarial Fever ....... 133 

Chart No. 11. Tertian Estivo-autumnal Malarial Fever 134 

Chart No. 12. Tertian Estivo-autumnal Malarial Fever 139 

Chart No. 13. Tertian Estivo-autumnal Malarial Fever . 140 

Chart No. 14. Tertian Estivo-autumnal Malarial Fever 143 

Chart No. 15. Tertian Estivo-autumnal Malarial Fever 144 

Chart No. 16. Subcontinued Estivo-autumnal Malarial Fever 163 

Chart No. 17. Combined Tertian and Tertian Estivo-autumnal Malaria . 164 
Chart No. 18. Combined Typhoid and Estivo-autumnal Malarial Fevers . 

176, 177 

Chart No. 19. Typhoid Fever (Decline) 189 

Chart No. 20. Acute Tuberculosis 190 

Chart No. 21. Infective Endocarditis (Dock) 193 



(ix) 



THE ESTIVO-AUTUMNAL (REMITTENT) 
MALARIAL FEVERS 



INTEODUCTION 

In the following pages it has been the aim of the author to 
describe minutely certain fevers as yet too little understood by 
the mass of the medical profession, and which are of the greatest 
interest, both from a scientific and a practical point of view. 
The author has approached his task with much hesitation, and 
only the assurance that, from a long experience with and study 
of the diseases in question, he may be able to do at least partial 
justice to them, prompts him to attempt their description. 

The work is very largely the result of personal experience 
gained in the United States military hospitals, and, as such, embod- 
ies the conclusions arrived at from nearly three years of inves- 
tigation and the careful study of hundreds of cases of the estivo- 
autumnal malarial fevers. A great majority of the cases have 
been malarias contracted in Cuba and in the Philippines, and 
it is believed that, whatever the shortcomings of the results ob- 
tained may be, the material for study has never been excelled. 

From the moment the author began the laboratory investiga- 
tion of the diseases prevalent in the troops, for the Medical De- 
partment of the United States army, he became convinced of the 
Vast importance of a thorough knowledge of the malarial fevers, 
and especially of the remittent malarial fevers, or, more cor- 
rectly, the estivo- autumnal fevers, to the practicing physician. 
At Chickamauga Park, where his first work was done, hundreds 
of cases of typhoid fever, pure and simple, were diagnosed as 
remittent malarial fever and treated as such, this being due very 
largely to the belief that because this camp was located in the 
south, it must necessarily become infected by malaria. As a 
matter of fact, there was but very little malarial fever present 
among the troops at Chickamauga Park, as has been amply 

A (1) 



2 ESTIVO- AUTUMNAL MALARIA 

shown by Vaughn, Dock, Reed, Shakespeare, and other inves- 
tigators. The colossal mistake of diagnosing hundreds of cases 
of typhoid fever as malaria was really responsible for the terrible 
epidemic which actually compelled the evacuation of the Park as 
a camping site. Because the mistake was due largely to igno- 
rance of the nature and methods of diagnosing the remittent 
malarial fevers, the author has felt it his duty to put upon 
record his experience with these fevers, together with that of 
others, in the hope that it may be of assistance to the profession 
at large. 

The charts shown are those of typical cases of the estivo- 
autumnal fevers, selected to demonstrate the variations in the 
temperature curve, variations that are often so puzzling that only 
the microscope can decide with what we have to deal ; and 
throughout the book I have consistently emphasized the infinite 
importance of the microscopical examination of the blood of all 
cases of fever, wherever they may develop. There can be no 
excuse to-day for the failure to diagnose either malarial fever or 
typhoid, for with the Widal test and the microscope we are armed 
with all that is necessary for their recognition. 



CHAPTER I 

DEFINITION OF THE REMITTENT MALARIAL FEVERS 
(ESTIVO-A VTUMNAL) 

GENEKAL KEMARKS 

Malarial fevers are of such wide distribution that a proper 
understanding of their etiology, symptomatology, and treatment 
is of the utmost importance to the medical profession. In our 
present advanced knowledge of the subject we know that these 
fevers are divided into three great classes; viz., the tertian, 
quartan, and estivo- autumnal malarial fevers, each caused by its 
own distinct blood parasite, and each presenting distinct and 
more or less characteristic symptoms. 

While the estivo -autumnal, or, as they are more universally 
known, the remittent forms of malarial fever, are more strictly 
bounded as regards distribution than are either the tertian or 
the quartan forms, they are so widely distributed as to make 
their recognition of the first importance, especially in view of 
the new fields opened to American colonization by the acquisi- 
tion of the Philippines, Porto Rico, and Cuba. In all three of 
these countries the remittent malarial fevers are endemic, es- 
pecially in Cuba and the Philippines, and will be found, as in 
all tropical countries, to be one of the greatest obstacles to their 
colonization. Malaria is a greater foe to civilization in the 
tropics than is any other one factor, and Koch* justly says: 
"Malaria is met with everywhere; the officer in his bureau, the 
traveler in the interior, the soldier upon the march, all must 
recognize that soon or late they are to become the victims of 
malaria." 

As the tropics are approached, we meet less often with the 
benign tertian and quartan fever and frequently with the more 
severe and resistant estivo -autumnal infections, which include 
also the terrible, pernicious malarial fever and the so-called black- 
water fever. So varied are the manifestations of this form of 
malaria that several distinct types have been described clinically; 

*"On Recognition, Cure, and Prevention of Tropical Malaria." 
(3) 



4 ESTIVO - AUTUMNAL MALARIA 

but all depend for etiology upon the presence in the blood of those 
forms of malarial plasmodia known as the estivo- autumnal para- 
sites or Plasmodia of Laveran. We may say, then, that estivo- 
autumnal or remittent malarial fevers are fevers caused by the 
presence in the blood of definite blood -parasites, and characterized 
clinically by paroxysms of fever of regular or irregular dura- 
tion, followed by regular or irregular intermissions or remissions. 
While this definition is very unsatisfactory, it is probably as de- 
scriptive of these protean fevers as any short definition could be, 
and will, at least, be of service as showing their main points of 
difference from tertian and quartan malarial fever. The par- 
oxysms and intermissions in the two last-named fevers are regular 
and definite in their phenomena, but in remittent malarial fevers 
this is often not so ; and while all three are caused by very nearly 
related blood -parasites, the remittent malarial fevers differ very 
widely clinically from the tertian or quartan fevers. Koch, in 
the article just referred to, has striven to prove that the estivo- 
autumnal fevers are essentially tertian fevers; but to one who has 
studied these forms of malaria thoroughly, his postulates are 
unsatisfactory and his array of evidence very far from convincing. 
I will speak of Koch's theories more fully later, but am convinced 
that they cannot be supported by facts, and that the estivo- 
autumnal fevers are far from being as regular in their manifesta- 
tions as he evidently believes them to be. 

Historical. — The earliest writings upon medicine describe 
more or less accurately the various types of malarial fevers, and 
it is probably true that the distinction between the benign tertian 
fever and the pernicious estivo - autumnal fever was well known to 
the ancient Greek and Roman physicians. This class of fevers was 
not known by the term "malarial" until after Torti distinguished 
them by their yielding to quinine in 1712. It may be said here, 
in passing, that the quinine test is not always to be relied upon 
in distinguishing these fevers, especially the estivo -autumnal 
fevers, and should never be used for diagnostic purposes if a 
microscopic examination of the blood can be obtained. 

Thayer, in his most excellent work, "Lectures on the Malarial 
Fevers," says: "To-day, however, in the light of our present 
knowledge, we are able to distinguish the malarial infections from 
other febrile processes, however similar their clinical manifesta- 
tions may be, not only by their behavior under treatment with 
quinine, but also by the presence in the blood of the specific para- 



GENERAL REMARKS 5 

site discovered in 1880 by Laveran." This fact may be said to 
be one of the greatest advances in modern medicine. 

A few of the older writers evidently had some idea of the 
parasitic nature of malarial fevers, for in 1846 Rasori wrote: 
"For many years I have held the opinion that the intermittent 
fevers are produced by parasites, which renew the paroxysm by 
the act of their reproduction, which recurs more or less rapidly, 
according to the variety of the species." 

The history of the discovery of the malarial parasite covers 
many years. Mitchell,* in 1849, claimed that the disease was due 
to spores found in marshy districts. In 1866, Salisbury t made 
himself famous by announcing the cause of malarial fevers to be 
certain vegetable cells, which he claimed to have found in the 
perspiration and urine of patients suffering from the disease. For 
a time his views were widely accepted. In 1879 Klebs and 
Tomassi Crudeli X found in the soil of malarial districts certain 
rod -shaped bacteria which, when injected into animals, in pure 
culture, were claimed by them to produce the symptoms of the 
disease. Their observations were never confirmed by careful 
observers, but for some time their views were accepted by a 
large portion of the scientific world. 

In 1880 Laveran, § a French army surgeon, stationed in Al- 
geria, after careful study of the blood of many cases of malarial 
fever, announced the discovery of a parasite in the blood which 
he had no hesitation in claiming to be the veritable cause of the 
disease. At first his researches attracted little attention, but they 
were soon confirmed by Richard, Marchiafava and Celli, Golgi, 
Councilman, Abbott, Sternberg, Osier, Dock, and other observers, 
and his claim to have discovered the actual cause of malaria 
abundantly verified. 

The reader is referred to Thayer's " Lectures on the Malarial 
Fevers " for an admirable history of the discovery of the malarial 
parasite. 

Laveran was the first investigator to recognize the relation of 
the parasites to the disease; but they had undoubtedly been seen 
before by both Meckel, in 1847, and Virchow, in 1848. The first 
observer mentioned noticed pigment in the blood obtained from 
a malarial patient, and that this pigment was contained mostly 

*"The Oryptogamous Origin of Malarious and Epidemic Fevers." 

t"Am. Jour. Med. Sci.,"Jan., 1866. 

jAreh. f. esp. Path. U. Paas. Mak, 1879, x. 1.311. 

I Bulletin de 1' Academie de Medecine de Paris, seance de 23 Nov., 1880. 



6 ESTIVO -AUTUMNAL MALARIA 

in round, ovoid, or spindle-shaped masses of protoplasm. He 
was probably the first observer to notice the ovoid and crescent 
forms of the estivo- autumnal organisms. 

Laveran noticed and described three forms of the parasite: 

a. Oval or crescentic bodies with hyalin protoplasm, contain- 
ing either a central or polar mass of golden yellow pigment- 
granules, arranged either in clumps or in a wreath -like arrange- 
ment. A faint hyalin bib could sometimes be seen connecting 
the extremities of the crescent. This form is easily seen to be the 
crescentic form of the parasite causing estivo -autumnal fever. 

b. Small, hyalin, rounded bodies containing a ring of pig- 
ment-granules which were motionless. Occasionally one of these 
bodies was seen with long, thin, hyalin filaments in active motion 
projecting from its circumference, while the pigment within it 
was also in rapid motion. 

This form is the flagellated form of the estivo -autumnal 
parasite, which will be described more fully later on. 

c. Spherical, slightly granular bodies, with immobile pigment 
— evidently degenerated forms of the two foregoing classes. 

From his observations he concludes that "there exist in the 
blood of malarial patients parasitic elements which have hereto- 
fore been confounded with melaniferous leucocytes; the presence 
of these parasites in the blood is probably the principal cause of 
the manifestations of paludism." 

Later, Richard* discovered the intracorpuscular hyalin para- 
sites and the segmenting bodies. 

Marchiafava and Celli, in 1885, described very carefully the 
hyalin intracorpuscular parasites, and proposed the term "Plas- 
modium malarias " for the parasite. Biologically this term is far 
from correct and should be abandoned. We are dealing with a 
parasite conceded by all competent observers to belong to the 
sporozoa, and having its principal habitat in the blood. The 
term Jicemamceba malarice, proposed by Welch, is more nearly cor- 
rect, and should be preferred to the term "Plasmodium." 

As, however, in the light of the most recent researches, the 
biological position of the malarial parasite would still seem to be 
in doubt, it would be better if in ordinary work the terms 
"tertian," "quartan," and "estivo -autumnal" malarial parasites 
were adopted, thus obviating all confusion regarding the exact 
status of the organism. 

*Gaz. med. de Par. 1882, 6 s. 4, 252. 



DISCOVERY OF THE PARASITES 7 

Golgi, in 1885, clearly showed that quartan fever depended 
upon a specific form of the malarial parasite, which he described 
and figured. Shortly afterwards he also described the specific 
parasite causing tertian fever. To him, likewise, we owe the dis- 
covery that the malarial paroxysm always coincides with the 
segmentation or sporulation of a group of parasites. This seg- 
mentation, occurring every forty-eight hours, produces tertian 
fever; while if it occurs every seventy -two hours, quartan fever is 
the type found. A quotidian fever is caused by the segmentation 
of two groups of tertian parasites which sporulate on successive 
days. 

Golgi's observations have been confirmed by Grassi, Canalis, 
Bastianelli, Bignami, Marchiafava, Celli, Mannaberg, Sakarov, 
Gotye, Sternberg, Osier, Dock, Thayer, Hewetson, and other 
eminent observers. 

DISCO VEEY OF THE ESTIVO- AUTUMNAL PARASITES 

Golgi, in 1885, was the first to call attention to the probably 
distinct type of the crescentic and ovoid parasite, and suggested 
the possibility of its being a new variety of the malarial organism; 
but to Councilman we owe the first statement of the diagnostic 
value of these forms. In 1887 he says: "The character of these 
bodies [the malarial parasite] varies in different forms of the 
disease. Although they seem in some eases to run into one 
another, still, in general, we can say that where the Plasmodia 
inside the red corpuscles are seen [large pigmented forms] the 
patient has intermittent fever, and where the crescentic and elon- 
gated masses are found he has either some form of remittent 
fever or malarial cachexia. . . . We are not only able to diag- 
nose the disease as such, but in most cases the particular form." 

Golgi, in 1889, was the first to observe that the small, hyalin, 
intracellular rings and the crescent and ovoid pigmented bodies 
were associated with malarial fevers of remittent character with 
long intervals between the paroxysms. He believed that the ring- 
forms were the first stage of the crescent and ovoid forms. 

The type of fever in which these organisms are found, and 
which is now known as estivo- autumnal fever, differs very materi- 
ally from the ordinary intermittent (tertian and quartan) fevers 
met with in northern latitudes. Under the term estivo -autumnal 
fever is included the majority of the cases of so-called pernicious 



8 ESTIVO- AUTUMNAL MALARIA 

malarial fevers, and their chief characteristics are their irregular 
paroxysms, protean clinical symptoms, and their greater resist- 
ance to quinine. In this class of cases, which are especially prev- 
alent in the malarial districts around Rome where they studied, 
Marchiafava and Celli, in 1889, discovered and described very 
minutely the appearance and life -history of the parasites con- 
cerned in their etiology. About the same time Canalis published 
the results of his investigations upon the parasites associated with 
irregular and remittent malarial fevers, and although his inter- 
pretation of some of the phenomena observed differed widely from 
those of Marchiafava and Celli, the morphological descriptions 
of the parasites were very similar, and confirmed Golgi's theory 
of the existence of a separate variety of the malarial parasite 
causing remittent malarial fever. A brief summary of the inves- 
tigations of the above-mentioned authors is here given. 

Marchiafava' s and Celli' s observations may be summed up as 
follows: For some time before an onset of a paroxysm of fever, 
three forms of the estivo- autumnal parasite may be seen in the 
blood, i. e., minute round or ring forms, having a small, dark 
center, composed of pigment or hemoglobin; intracellular, mi- 
nute, amoeboid, hyalin parasites, containing one to three small 
pigment -granules, and somewhat larger round bodies having a 
block of pigment at some portion within them. The red cor- 
puscles containing the parasites were seen to be smaller than the 
surrounding corpuscles, darker green in color, and crenated, 
while the hemoglobin was often seen to be retracted from the 
periphery of the corpuscle for a whole or part of its circumfer- 
ence. Segmenting bodies were very rarely seen in the circulating 
blood, but were found in large numbers in the internal organs, 
especially the spleen and the capillaries of the brain. They 
observed that pigmentation always occurred before the onset of a 
paroxysm, and that the parasites pursued a developmental cycle 
of twenty -four hours or less. At the time of the paroxysm, and 
for some time afterwards, the small amoeboid hyalin parasites, 
which comprise the new generation, may be seen in the blood. 
They describe the crescentic organisms and also intervening forms 
between the intracellular bodies and the crescents. They note 
the minuteness of the estivo -autumnal parasite as compared with 
the tertian and quartan forms. They found the crescents in greater 
number in the spleen, but observed many cases without the 
formation of crescents. No segmentation of the crescents was 



FORMS AND DEVELOPMENT 9 

ever noticed, and neither is the development of pigment always 
to be observed. In those fevers in Rome showing daily paroxysms 
only the small, hyalin, amoeboid, intracellular parasite is observed 
in the peripheral blood, and only in those cases showing a longer 
interval between the paroxysms is the parasite with the few 
pigment -grains to be seen. 

Canalis' article is a very elaborate one. He divided the cycle 
of development into two phases: a rapid cycle, and a slower 
cycle in which the crescentic forms appear. The rapid cycle he 
considers to be of about two days' duration, though it may be 
only twenty -four hours in length. During the first hours the 
parasites are intracellular, amoeboid, hyalin, occupying one -sixth 
of the red corpuscle, the outer portion of the parasite being 
clear, while the center appears shaded or greenish, presenting the 
appearance of a nucleus. The outer portion may be very refrac- 
tive. The blood -corpuscles which they have invaded are very 
often smaller than normal and are greenish in color. As the 
parasite grows it becomes more amoeboid, and a few fine particles 
of reddish brown pigment may be seen within the outer ring -like 
portion. The parasite gradually grows larger, the ring-like ap- 
pearance disappears, the amoeboid movement ceases, the pigment- 
granules melt into one small solid block at the center, or one 
side of the parasite, and a faint radial striation appears, and 
from six to ten ovoid or round segments are eventually pro- 
duced. They are much smaller than the segments of tertian or 
quartan fever. The containing corpuscle may be entirely disin- 
tegrated or may appear as a dim, shadowy sphere surrounding 
the segments. Segmenting bodies are very rarely seen in the 
circulating blood, but free pigment and pigmented leucocytes are 
common. 

The second, or slow, cycle, in which crescents develop, may 
occur in connection with the rapid cycle, or where the course of 
the disease has been interfered with by some drug, especially 
quinine. Canalis always found that crescents were not developed 
until some time after the onset of the fever, generally not until 
fifteen days had elapsed. The small, intracellular, amoeboid forms 
were observed to become oval in shape, while the pigment col- 
lected toward the center ; a crescentic form was gradually acquired ; 
the red corpuscle disappeared, and the now fully formed crescent 
was set free in the blood. He observed the double outline of 
the crescent, and considered that it was due to an enveloping 



10 ESTIVO- AUTUMNAL MALARIA 

membrane. The crescents were afterwards observed to acquire 
an oval form and finally become perfectly round. In the cres- 
centic and ovoid forms the pigment was always motionless, but 
in the round form it often became very mobile, and was arranged 
in a perfect circle. He describes a process of sporulation as 
occurring at this time from the second bodies. The segments 
are round or oval. He distinguishes this process from a degen- 
erative process which often occurs, as follows: "In this degener- 
ative process one meets with bodies which have lost their yellow- 
ish or ashy color and have became clearer, sometimes refractive, 
with a double contour much more marked than that of the ordi- 
nary parasite, while their substance is transformed into a mass 
of round or irregular bodies of various sizes and with a single 
contour. If one continues the microscopic examination of one of 
these parasites during the course of several minutes, he may 
sometimes see that two or three of these spherules become united 
with a single body, thus forming irregular masses which, contin- 
uing the process of fusion, finally give to the parasite a homo- 
geneous aspect without trace of spherules. 

"The pigment is sometimes arranged as a central crown, 
sometimes scattered irregularly at an extremity or at one side of 
the body. The points which distinguish this process from that 
of sporulation are: the refractiveness of the degenerating body; 
the irregularity in size of the spherules; the absence in these 
spherules of a more opaque central area; their fusion into irreg- 
ular bodies and finally into an amorphous mass." 

He also observed the development of flagellate bodies from 
the round bodies, and of them he says : "They represent, assur- 
edly, one of the last stages in the development of the parasite, 
for I have never seen them appear in the blood before the 
formation of the round bodies." 

Canalis considered the length of this cycle to vary, the period 
from the amoeboid stage to the crescentic lasting from three to four 
days, the development of the round bodies taking a day longer. 

In this truly admirable paper it is unfortunate that the 
author committed himself to the sporulation theory of the cres- 
cents, for in the light of our present knowledge such a theory is 
untenable, and no modern investigator has ever observed the 
sporulation of a crescentic organism. 

That a distinct type of parasite is always associated with the 
estivo- autumnal fevers has been confirmed by every intelligent 



FURTHER RESEARCH 11 

investigator, and Bignami, Sanfelice, Phlen, Mannaberg, Dock, 
Thayer, Hewetson, and the author have confirmed much that 
appeared in the articles of Marchiafava, Celli, and Canalis; but 
there is yet much diversity of opinion as to the classification of 
the forms observed. 

Marchiafava and Bignami have very thoroughly investigated 
the parasites occurring in the estivo-autumnal fevers, and, as 
the result of their studies, have separated these parasites into 
two varieties, one causing a paroxysm every twenty-four hours, 
the other every forty-eight hours, approximately, and which they 
have termed the quotidian and malignant tertian estivo-autumnal 
organisms. The fever caused by the quotidian parasite may be 
regular and resemble the ordinary double tertian paroxysm, but 
more often the temperature curve shows evidence of anticipation 
or retardation, being irregular, and the symptoms vary much in 
their severity. A continuous or slightly remittent fever is not 
unusual. The quotidian parasite, as described by them, is gen- 
erally seen as a very small, amoeboid, hyalin, ringlike, intracor- 
puscular body, in the circulating blood, which prior to seg- 
mentation develops a small number of minute pigment/- gran- 
ules. Segmentation generally occurs within the red corpuscle, 
and almost always in the internal organs, especially in the 
spleen. The rings are very pale and often require very careful 
search before they are discovered, are actively amoeboid, and 
never exceed one -third of the corpuscle in size. The infected 
corpuscle has a greenish, brassy color, is often shrunken, and 
the hemoglobin retracted. After some days crescentic and ovoid 
bodies appear. 

Marchiafava and Bignami' s malignant tertian parasite pro- 
duces a febrile paroxysm lasting from twenty -four to forty 
hours, and often the temperature curve shows such variations, 
caused by the anticipation and conjunction of paroxysms, as to 
present a continual fever. According to them the febrile curve 
presents, in the majority of cases, the following characteristic 
points : rapid and sudden rise, a stationary stage, with slight re- 
missions, a slight pseudocrisis, a precritical rise, marked often 
by the highest temperature, and at last a sharp crisis during 
which the temperature often falls far below normal. Very often 
the temperature curve is very irregular, due, as quoted by Thayer 
and Hewetson,* to the following influences : 

* "Malarial Fevers of Baltimore," Johns Hopkins Hospital Reports, Vol. V. 



12 ESTIVO- AUTUMNAL MALARIA 

1. By modification of the curve in the individual paroxysms. 

2. By modification in the succession of the paroxysms. 

A. The important modifications of the curve are the follow- 

ing : 

a. The lack of a sharp initial elevation, so that the curve 

rises in a progressive and continuous manner. 

b. The exaggeration of the pseudocrisis so that the at- 

tack tends to lose its individuality. 

c. The prolongation of the paroxysm, which is usually as- 

sociated with an exaggeration of the thermic oscilla- 
tions during the fastigium. 

d. The lack of a sharp precritical elevation. 

B. The modification in the succession of the paroxysms 

may be: 

a. The anticipation of the paroxysms, which can occur in 

the mild as well as the severe forms. 

b. The retardation, which can occur also in the grave 

infections. 

c. The prolongation of the paroxysms, by which apyrexia 

is made incomplete. 

d. The presence of slight oscillations in the temperature 

during the period which ought to be one of apyrexia. 

e. The reduplication of the attacks. 

Quinine will also cause important modifications in the tem- 
perature curve. 

The malignant tertian parasite, as described by these authors, 
resembles the quotidian very closely, but is larger and presents 
a greater amount of pigment within its protoplasm. It is often 
one -half the size of the red blood -corpuscle. Like the quotidian, 
segmentation takes place mostly within the vessels of the internal 
organs. The infected corpuscles are almost invariably shrunken, 
dark green in color, and often crenated and degenerated. Cres- 
centic and ovoid forms appear after a few days. 

The difference between the quotidian and malignant tertian 
estivo- autumnal parasites, as given by Marchiafava and Bignami, 
and tabulated by Thayer and Hewetson,* are as follows: 

1. The length of the cycle of development, which in the quo- 
tidian parasite lasts about twenty-four hours, and often 

*"The"Malarial Fevers of Baltimore," Johns Hopkins Hospital Reports, Vol. V. 



TWO VARIETIES EXIST 13 

occurs without the development of pigment, while in the 
tertian it lasts forty -eight hours, and is always associated 
with pigmentation. 

2. The size of the amoeba; in the same relative stage of develop- 

ment the amoeba of tertian fever is generally larger and 
of a more transparent appearance. 

3. The movements, which in the tertian parasite are retained 

for a longer time by the larger pigmented forms than in 
the quotidian parasite; they are also more active in the 
tertian organism. 

4. The length of the amoeboid unpigmented stage, which, in 

the tertian body, may last more than twenty -four hours. 

5. The time elapsing after the beginning of the new paroxysm, 

before the appearance of the new generation of parasites, 
which, in the tertian fever amounts to several hours, con- 
siderably longer than with the quotidian type. 

Mannaberg distinguishes three varieties of the estivo- autumnal 
parasite — an unpigmented quotidian, a pigmented quotidian and 
the malignant tertian parasites. Grassi and Feletti also describe 
the pigmented and unpigmented quotidian parasites. In 1893 
Golgi published his researches concerning the parasite of estivo- 
autumnal fever, in which he vigorously combated the existence 
of more than one variety of the estivo -autumnal organism, and 
stated that the forms found in the circulating blood were chiefly 
accidental, the infection being present almost entirely within the 
internal organs. 

Gautier, Korolko, Zieman, Dock, Thayer, and most of the 
American authorities, accept only one variety of the estivo- 
autumnal parasite. My own views upon this subject will be 
given in detail in the next chapter, but a large number of ob- 
servations have convinced me that two varieties of the estivo- 
autumnal parasite do exist, and can be demonstrated where the 
clinical material is available. Wilson and Ashton* say regard- 
ing the estivo -autumnal parasite: "Its development is accom- 
panied with more irregularity than that which attends the other 
varieties of parasites, and while clinically it may be possible 
in the milder instances of infection to recognize certain types, 
such as quotidian and tertian, the type is so confused as to ren- 
der its analysis almost impossible." This statement is too radical, 

*" Encyclopedia of Medicine," Sajous, p. 465. 



14 ESTIVO- AUTUMNAL MALARIA 

for study of this class of malaria will convince any one that the 
quotidian and tertian estivo- autumnal fevers do exist, can be 
easily recognized if quinine is withheld, and that each is caused 
by its own characteristic parasite. 

Quite recently Sternberg and Munson have, in their writings, 
classed the estivo -autumnal parasites in two divisions, the quo- 
tidian and tertian, thus following Marchiafava and Bignami's 
classification. Thorough study of the blood and the clinical 
manifestations in the estivo -autumnal malarial fevers has not 
received the attention which the importance of the subject de- 
serves, especially in this country, due very largely to the com- 
parative rarity of these types of malarial fever, but, as stated 
before, research along this line will prove conclusively the truth 
of Marchiafava and Bignami's deductions regarding the estivo- 
autumnal malarial fevers.* 

*"Popular Science Monthly," Feb., 1901 ; "Military Hygiene," 1901. 



CHAPTER II 

THE DESCRIPTION OF THE PARASITES CAUSING THE REMITTENT 
( ESTIFO - AUTUMNAL) MALARIAL FEVERS— THE QUOTIDIAN 
ESTIVO- AUTUMNAL PARASITE — THE MALIGNANT TERTIAN 
ESTIFO- AUTUMNAL PARASITE 

Before describing the parasites concerned in the etiology of 
this form of malaria, a few words regarding the course of the 
temperature curves is in place. While we may, and often do, 
have, in patients who have been taking quinine, the most irreg- 
ular and uncharacteristic temperature-curve pictures, occurring 
with remittent malarial fever, still, in the tropics, and in uncom- 
plicated cases in this country, the temperature curve in the 
great majority of cases conforms to one of two types, i. e., a 
quotidian or tertian paroxysm, with intermissions. In the quo- 
tidian estivo- autumnal fever the temperature curve resembles 
very closely that of an ordinary double tertian, there being a 
sharp daily rise followed by a remission or, generally, an inter- 
mission. This type of estivo -autumnal fever embraces a large 
portion of those cases showing pernicious symptoms, and is 
much more rare than is the tertian type. 

The tertian type of remittent malarial fever, as observed by 
me, is marked by a very characteristic temperature curve, is 
the most common form of the disease, and corresponds to 
Marchiafava and Bignami's malignant tertian fever. Many ob- 
servers, especially Koch, consider all cases of estivo -autumnal 
fever to belong to this type; and while this may be true of 
the cases studied by them, all cases of the disease can by no 
means be so classified. The temperature curve exhibited by this 
form of the disease may be briefly analyzed as follows: A 
rapid and sudden rise, a stage with slight remissions, a pseudo- 
crisis, a precritical rise, in which the temperature goes above 
the highest point previously reached, and, lastly, the true crisis, 
in which the temperature falls rapidly below normal. We may 
have great irregularities and variations in both these forms, 
due to causes which influence the temperature in any febrile 
disease; but the majority of cases will be found to conform to 

(15) 



16 ESTIVO- AUTUMNAL MALARIA 

these types. A great source of fallacy in our study of malaria 
lies in the difficulty of getting the cases before quinine has 
been administered ; the administration of this drug interferes 
very markedly with the true course of the temperature curve, 
and is the chief reason why most observers in this country 
have been unable to demonstrate the existence of quotidian and 
tertian remittent malarial fever, in studying the malarial fevers 
so common among our soldiers returning from Cuba. If qui- 
nine is stopped in such cases, however, the fever is almost sure 
to recur soon, and will, in time, exhibit the characteristic curve. 
The study of hundreds of cases of malaria in soldiers return- 
ing from Cuba and the Philippines, and of a large number of 
cases in Cuba, has convinced me of the truth of the facts stated, 
and though I realize that many authorities may differ with me, 
I can only say to such : Study the disease uncomplicated by 
quinine and in its native habitat, as in Cuba, and there will 
remain no doubt, even in the mind of the most skeptical, of 
the truth of the observations noted in this chapter. 

It should not be forgotten that in many instances, especially 
in the tropics, a combined infection may be present of both 
varieties of the parasite, and of course both may be found in the 
blood in different stages of development. Such cases have been 
largely to blame for the confusion which has existed regarding 
these parasites. 

In ordinary tertian and quartan malarial fever we have no 
difficulty in following the various stages of the development of 
the parasites in the circulating blood ; but in the estivo- autum- 
nal fevers this is not so, as only the hyalin and slightly pig- 
mented bodies are present in the circulating blood, and in order 
to study the larger pigmented and segmenting forms it is neces- 
sary to obtain blood by puncturing the spleen. This is a 
dangerous and generally unnecessary procedure, so far as diag- 
nosis is concerned, for the forms found in the circulating blood 
are sufficient for such purposes ; but for the scientific study of 
the parasites the procedure is necessary, and if due precautions 
are used, the danger is very slight. 

The remittent or estivo -autumnal malarial fevers, like tertian 
and quartan malarial fever, are due to blood parasites, having 
two life-cycles. One cycle, that in which we are most interested, 
is completed in man; the other, hardly less interesting and 
probably more important from a prophylactic standpoint, is 



STAGES IN LIFE OF PARASITE 17 

completed in insects, limited, so far as our present knowledge 
extends, to mosquitoes. 

In man the development and growth of the parasites causes 
the complex symptom-picture known as malaria, and after the 
parasite has reached a certain stage of development in man it is 
taken up by the mosquito, in whose intestine it undergoes certain 
other changes, and finally becomes lodged in the venomo- salivary 
glands of the insect, from which it again reaches man when the 
insect bites. 

It is my purpose in this chapter to describe certain stages in 
the life-cycle of the estivo-autumnal parasites in the human 
body, reserving for the next chapter the consideration of the 
special forms of the parasites having to do with the life -cycle 
in the mosquito. 

In the description of the estivo-autumnal parasites I shall 
divide the subject as follows: (1) The quotidian estivo-autumnal 
parasite — the hyalin body, the pigmented body, the segmenting 
body; (2) the malignant tertian estivo-autumnal parasite — the 
hyalin body, the pigmented body, the segmenting body. 

The Quotidian Estivo- Autumnal Parasite.— The Hyalin 
Bochj. — This form of the malarial parasite completes its develop- 
ment in twenty-four hours, as a rule. The parasite appears 
first as a very minute (.5 to 1 p in diameter) ring-shaped or 
round hyalin body, actively amoeboid, within the red blood - 
corpuscle. The outline of the organism is very indistinct and, 
were it not for its active amceboid movement, it would be very 
easily overlooked. The ring form is usually perfectly circular 
when at rest, the center appearing of the same color as the 
corpuscle within which it lies ; the organism is not very refrac- 
tive and its outline is not sharply cut. When in motion it 
often appears triangular in shape, the movement consisting of 
a rapid, wavy motion of its border and the shooting out of 
minute protoplasmic prolongations which are retracted almost as 
quickly as thrown out. The motion is not sluggish, but very 
rapid. Sometimes the ring form is lost, the organism becoming 
a pale hyalin disc. The movement is very erratic, and there 
are long periods of repose during which the ring form is re- 
tained. The prganism is very small and never grows to occupy 
more than one- sixth of the corpuscle. The corpuscle containing 
the parasite is smaller than those surrounding it, presents a 
shrunken, wrinkled appearance, and is dark green in color. 



18 ESTIVO- AUTUMNAL MALARIA 

Often two or more parasites are seen within one corpuscle. 
There is no signet-ring appearance, so common in the malignant 
tertian parasite. It is in this form of estivo- autumnal fever 
that the red corpuscles are most rapidly destroyed, and in per- 
nicious cases almost every corpuscle in a microscopic field will 
be seen to contain a parasite. While the amoeboid movement is 
not as constant as in the tertian parasite, it is more rapid and 
has to be watched for carefully. 

The features to be noticed in the hyalin stage of the quo- 
tidian estivo- autumnal parasite are: its minute size (never more 
than one-sixth the size of the red corpuscle), its indistinct 
outline and the rapidity of its movement. This stage is seen in 
the circulating blood best during or immediately after a paroxysm. 

The Pigmented Stage. — Just prior to pigmentation the par- 
asite becomes a little larger, loses its ring form, becomes more 
refractive and sharply defined, much more so than is the malig- 
nant tertian parasite. In this parasite I have never observed a 
pigmented ring, the rule being that before pigmentation the 
ring form is lost. The pigment appears as a single, or at most 
two, granules, either in the center or at one side of the parasite, 
and is always perfectly motionless. Sometimes the pigment ap- 
pears as a rather coarse, irregular block situated in the center of 
the parasite, and I have considered such an appearance as denot- 
ing the approach of a segmentation. The infected corpuscle is 
always shrunken, greenish in color, and often crenated. Often, 
also, the hemoglobin seems to have retracted around the parasite. 
At this stage it is never more than one -fourth the size of the 
corpuscle. The chief points of interest at this stage are : loss 
of ring form before pigmentation, lack of motion of pigment- 
granules, changes in the infected corpuscle. Pigmented forms 
are by no means rare in the circulating blood, and are most 
numerous just before or during a paroxysm. The pigment is 
dark red or black in color. Amoeboid motion is lost. 

The Segmenting Body. — This stage is rarely observed in the 
circulating blood. I have only observed segmenting bodies three 
times in over one hundred cases of quotidian estivo -autumnal 
fever, and only in the pernicious type. In blood from the spleen, 
or in smears from that organ, taken after death, segmenting 
forms are common. In the parasite which has become pig- 
mented, little change is noticed prior to segmentation, save that 
the pigment is collected in a solid block at the center of the 



PRESENCE OF QUOTIDIAN PARASITES 19 

organism, while its protoplasm has become very finely granular in 
appearance. The pigment may be situated at one side, and the 
parasite is always round or oval in shape. As segmentation 
commences, faint radial striations can be detected starting from 
the center, and soon the organism breaks up into from six to eight 
minute round or oval segments. "Marguerite" forms are rare, 
irregular segmenting forms being the rule. A peculiarity of the 
process of segmentation in this form of the parasite is that it 
occurs generally inside of the red corpuscle before its entire 
destruction. In all 'the cases in which I have observed segment- 
ing forms in the circulating blood, segmentation has occurred 
within the corpuscles, and this is one of the characteristic phe- 
nomena observed in the life -cycle of the quotidian estivo- autum- 
nal parasite. The segmenting bodies are most common just 
before or during a paroxysm. 

The chief points of interest at this stage are : The granular 
appearance of the parasite, the occurrence of segmentation within 
the red corpuscles, and the small number of segments. 

Presence of the Quotidian Parasites in the Blood in Relation 
to the Attack. — During the acme of the elevation of the tempera- 
ture and the sweating stage the small amoeboid parasites are 
found in the blood within the red corpuscles. The number of 
infected corpuscles varies greatly, some cases showing only one 
or two in the whole specimen, while in others every microscopic 
field will show several. At this stage the parasites are always 
unpigmented, and often show no amoeboid motion for longer or 
shorter periods of time. 

During the afebrile stage the blood will show, besides £he ring 
forms, a few or many, as the case may be, small pigmented 
bodies, generally circular in shape and containing one or two 
small pigment dots. 

Just before the onset of the paroxysm, and often during the 
initial rise of the fever, larger pigmented forms are present, the 
pigment generally being collected near the center of the parasite, 
while the infected corpuscles are very brassy in appearance. The 
segmenting forms, as has been noted, are only very rarely seen 
in the circulating blood. In typical cases of quotidian estivo- 
autumnal fever, or where there is infection with more than one 
group of parasites, the presence of the various forms in the 
blood becomes irregular, and hyalin and pigmented forms may be 
observed at almost any time; but there will always be found a 



20 ESTIVO -AUTUMNAL MALARIA 

greater number of forms which correspond to the" stage of the 
disease, as shown by the clinical chart. Often in a double infec- 
tion only a very few parasites belonging to one group will be 
seen, while there are multitudes belonging to the other group 
present, and it will invariably be found that it is the most nu- 
merous group which is responsible for the clinical symptoms. 

It is this form of the estivo- autumnal parasites which is most 
often found in the pernicious forms of the disease resulting fatally, 
but it is rare when compared to the form to be described next. 
The great majority of the cases of remittent malaria occurring in 
our soldiers in Cuba and, as far as I have observed, in those 
returning from the Philippines, were caused by the malignant 
tertian form of the parasite; but now and again, a pure case 
of quotidian fever would present itself, and the characteristic 
parasite could always be demonstrated when quinine had not 
been administered. 

The Malignant Tertian Estivo- Autumnal Parasite. — This 
is the most common parasite associated with estivo -autumnal 
fever, and is the one which has been most studied and is best 
known. The reason for this is not hard to find. The majority 
of cases of estivo -autumnal fever, especially in this country, are 
due to this parasite, and even in those cases in which the quo- 
tidian parasite has occurred, it has probably been in conjunction 
with the tertian, as those who read the varied descriptions of the 
parasite of estivo -autumnal fever will be forced to admit. 

The Hyalin Stage. — Like the quotidian parasite, the first 
stage in the development of the tertian organism consists of a 
round hyalin ring or disk, but several important differences are 
to be noted, i. e., the ring is larger, being from one -third to 
one -quarter the size of the corpuscle; it is irregular, presenting 
an enlargement at some portion of its circumference, giving it 
the so-called signet -ring appearance; it is highly refractive and 
is sharply cut, looking as though it had been punched out of the 
corpuscle; its protoplasm is clear and homogeneous: its amoeboid 
movements are slow and sluggish as compared with the quotidian 
parasite. The ring form is often lost, a clear hyalin disk result- 
ing. The changes in outline are very marked, and it is much 
easier recognized than is the quotidian parasite. Only very rarely 
does more than one organism invade a single corpuscle, as is 
common in the quotidian form. The infected corpuscle is greenish, 
and smaller, but is not so markedly affected as in the quotidian. 



PRESENCE OF TERTIAN PARASITE 21 

The Pigmented Stage. — In the course of twenty to twenty- 
four hours, during which time the hyalin body has been amceboid, 
a few fine pigment -granules make their appearance within the 
ring, generally in the enlarged area at one portion of its circum- 
ference, thus giving the organism a still greater resemblance to 
a signet-ring; the amoeboid movement continues, and the pigment- 
granules themselves are often seen to be in rapid vibratory motion. 
The pigment is reddish in color, and is present in larger amount 
than in the quotidian parasite. The organism gradually loses 
its ring form and becomes larger, sometimes occupying one-half 
of the corpuscle ; at the same time, it becomes more clearly 
defined, its protoplasm more refractive and faintly granular in 
appearance. The amoeboid motion still continues, though very 
sluggishly, and the pigment tends to collect in a solid block, 
which has a marked vibratory movement. The pigmented form 
is somewhat rare in the circulating blood, but blood from the 
spleen will show immense numbers of them. The chief points 
of interest are: appearance of pigment in the ring form, sharply 
cut outline and granular protoplasm, mobility of the pigment- 
granules, and larger size. 

The Segmenting Stage. — In about forty -eight hours the para- 
site has grown to be one -half to two -thirds as large as the 
red corpuscle, the pigment has become motionless and collected 
in a block near the center, and distinct radial striations are vis- 
ible. The segments are larger than those of the quotidian organ- 
ism, are more oval in shape, and number from ten to fifteen or 
more. The segmentation usually occurs outside of the corpuscle. 
I have observed segmenting bodies but once in the circulation. 
The parasite is very refractive, sharply outlined, and the proto- 
plasm is granular. 

One of the most characteristic features of the malignant ter- 
tian parasite, after the ring form has been lost, is the peculiarly 
refractive, finely granular appearance of its protoplasm, resem- 
bling very closely that of the crescents. The pigment is also in 
finer particles, but there are more of them. 

Presence of the Tertian Estivo- Autumnal Parasite in the Blood 
in Relation to the Attack. — During the acme of the temperature 
and until the afebrile stage is reached, the small non- pigmented 
hyalin, amoeboid ring forms or disks are found in the circu- 
lating blood, with occasionally, at the acme of the fever, a 
larger pigmented body. 



22 ESTIYO- AUTUMNAL MALARIA 

During the afebrile stage, the ring forms gradually develops 
pigment, and the nearer the time of onset of the paroxysm ap- 
proaches, the larger and more numerous do the pigmented forms 
become. Just before the paroxysm, the blood will probably show 
a few pigmented forms, occupying from one -half to two -thirds 
of the corpuscle, which is brassy in color, the hemoglobin often 
being retracted around the parasite. The pigment in such para- 
sites is usually collected at the center, and is immobile. Often 
at the commencement of a paroxysm the blood from the ear or 
finger will show no parasites and but a few pigmented leucocytes. 
However, if the blood be examined when the attack is at its 
height, i. e., when the fever is highest, numerous ring forms 
will be found. Although segmenting forms can be readily found 
at the onset of a paroxysm in blood from the spleen, they very 
rarely occur in the blood taken from the ear or finger. Very 
many cases, both of quotidian and tertian estivo- autumnal fever, 
will be found which show at most but very few pigmented para- 
sites in the peripheral blood, and often, if the blood be examined 
but once, none at all will be found, though a few ring forms 
can always be found, provided they are looked for at the proper 
time, and the examination persisted in. Nowhere does one dis- 
cover the fact that " patience is a virtue " more quickly than in 
examining the blood of cases of estivo -autumnal fever. Often a 
half hour will be spent before a parasite is found, though in the 
majority of cases so long a search is not necessary. In estivo- 
autumnal fever, the parasites are always most numerous during 
the apyrexial stage; but there are often seen mild cases of the 
disease in which, only after tedious and repeated examinations of 
the blood, will the parasites be found. In such cases pigmented 
leucocytes are almost always present, and it is justifiable to make 
the diagnosis of malaria from them alone. 

The summary given may serve to make more clear the differ- 
ences between the quotidian and malignant tertian estivo- 
autumnal parasites. 

I would say that from my observations of the estivo- autumnal 
malarial fevers in this country and Cuba, comprising both mi- 
croscopical and clinical study under exceptional conditions as 
regards opportunity and material, I am forced by the logic of 
facts to confirm Marchiafava and Bignami's conclusion regard- 
ing this type of malarial fever. There undoubtedly exist two 
varieties, at least, of the malarial parasite giving rise to these 



LIFE- CYCLE AND DEVELOPMENT 23 

fevers: one having a cycle of development of twenty-four hours 
and giving rise, in uncomplicated cases, to a fever having quo- 
tidian paroxysms; the other having a life -cycle of forty -eight 
hours, and giving rise to a fever with tertian paroxysms, in which 
the temperature curve is peculiar and characteristic. 



Stage of Development. 


Quotidian. 


Malignant Tertian. 




Size 


Minute % of corpuscle. 


Larger % to M of cor- 
puscle. 




Shape 


Ring or perfectly round. 


Signet-ring shape. 




Motion 


Very active. 


Sluggish. 




Outline 


Indistinct. 


Clear cut and refractive. 


The hyalin body. 


Blood - cor - 


Very dark green wrin- 


Light green, less wrin- 




puscle,... 


kled. Crenated. 


kled. 




Number 


More than one parasite 


Very seldom more than 






in a corpuscle, com- 


one parasite in a cor- 






mon. 


puscle. 




Size 


M size of corpuscle. 


Vi size of corpuscle. 




Shape 


Bound. Loses ring 


Ring form becomes pig- 






form before pigmen- 


m e n t e d , afterwards 






tation. 


the parasite is round. 




Motion 


Amoeboid motion is lost. 


Amoeboid motion contin- 
ues. Is sluggish. 




Outline 


More sharply defined. 


Very sharply denned, 
and refractive. The 


The pigmented 






protoplasm firmly 


body. 






granular. 




Pigment ... 


One or two coarse gran- 


Several minute grains, 






ules, perfectly mo- 


having a rapid vibra- 






tionless. 


tory motion. 




Number 


May be more than one 


Never more than one in 






in a corpuscle. 


a corpuscle. 




Corpuscle . . 


Very green in color, 


Lighter in color, seldom 






often crenated. 


crenated. 




Place of 


Within the red blood- 


Outside the red blood- 




segmenta- 


corpuscles, as a rule. 


corpuscles, as a rule. 


The segmenting 


tion. 






body, 


Number of 
segments. 


Six to eight. 


Ten to fifteen, or more. 






Crescents small and 


Crescents long, narrow, 


The crescent 




plump, containing 


deeply pigmented. 


phase. 




small amount of pig- 


Double outline less 






ment. Always pre- 


common. 






sent double outline. 




Cycle of develop- 
ment. 




Twenty-four hours. 


Forty-eight hours. 



CHAPTER III 

THE CRESCENTIC, OVOID AND FLAGELLATED FORMS OF THE 
ESTIVO- AUTUMNAL PARASITES* 

So far I have considered the forms of the estivo- autumnal 
parasites which belong properly to the life -cycle of the organ- 
isms within the human body. The crescentic, ovoid and flagel- 
lated forms now to be described are those phases of the parasite 
which, as Marchiafava well says: "begin in man the life-cycle which 
is completed in the mosquito." In the next chapter I shall con- 
sider fully the mosquito cycle of the estivo -autumnal parasites, 
together with the experimental data which has accumulated con- 
cerning this most interesting and important etiological question. 

Time of Occurrence of Crescents and Ovoids. — After infec- 
tion with the estivo -autumnal parasites has persisted for a cer- 
tain length of time, peculiar endoglobular bodies appear in the 
circulating blood, which, from their morphological peculiarities, 
are known as crescentic and ovoid bodies. As to the exact 
time in which the crescents appear authorities differ somewhat. 
Canalist says that he has never but once seen crescentic bodies 
in the blood before the fifteenth day of the disease, but most 
other authorities claim that they occur after the disease has per- 
sisted a week or more. From my own observations I believe 
that they may occur in the peripheral blood as early as the 
seventh day of the disease, and if splenic blood be examined, 
much earlier, even by the fourth or fifth day. Crescents occur 
only in the blood of patients suffering from the estivo - autumnal 
fevers. 

Description of the Crescents. — These forms of the estivo- 
autumnal parasite, as their name implies, are crescentic in shape, 
being smaller at their extremities than in the middle. They 
are longer than the diameter of the blood -corpuscle, and are 
always endo- globular. All stages in the development of the 

*A portion of this chapter is taken from an article by the author in the "New York 
Medical Journal " for Dec. 23, 1899. 

tCanalis,"Studi sull' inflezione malarica. Siomale medici del esereito e della marina." Dec, 
1889, p. 1329. 

(24) 



THE CRESCENTS 25 

crescent within the blood -cell have been observed, and will be 
considered later. When fully developed, the crescents are 
beautifully typical in shape, having a very refractive, more or 
less finely granular protoplasm, and containing within them, 
generally at the center, but often at one or the other pole, a 
clump of pigment which is usually in the form of slender rods 
or round dots. This pigment is dark in color. In the young 
crescents the pigment is distributed throughout the protoplasm 
but becomes collected at the center or one end as the crescent 
matures. The border of the crescent is sharply cut, being 
represented by a single or double line which has a peculiar 
greenish color. In most crescents, when fully grown, careful exami- 
nation will show a dim line upon the concave side of the crescent 
connecting the two horns. Often this "bib," as it is called, has a 
distinct yellowish green tinge, showing it to be, as is the case, 
the remains of the red blood-corpuscle in which the crescent was 
developed. The greenish tinge of the border of the crescents is 
due to the hemoglobin of the red cell which has retracted about 
it, and formed an enveloping membrane. The finer structure 
of the crescent will be considered in the description of the stain- 
ing reaction of the parasites. 

Distinction Between the Crescents of the Tertian and Quotidian 
Estivo- Autumnal Parasites.— Crescents are developed in the life- 
cycle of both varieties of the estivo -autumnal parasites, and their 
morphology differs in a few particulars. The tertian estivo - 
autumnal crescent is large, very slender, with pointed extremities, 
very refractive and seldom shows a double outline. Its proto- 
plasm is finely granular, and the pigment large in amount and 
in the form of slender rods. 

The quotidian estivo -autumnal crescent is much shorter and 
plumper than is the tertian, sometimes being very small. Its 
extremities are never pointed, but instead are rounded, and it 
always presents a distinct double outline. The protoplasm is less 
granular, and the enclosed pigment is smaller in amount and in 
the form of dots. 

As a rule, the pigment within both forms of crescents is im- 
motile, but I have seen sluggish motility in the pigment in a 
few instances. 

Crescents undergo certain degenerative changes, the most com- 
mon of which is vacuolization. Such crescents become altered in 
shape, less refractive, and throughout their protoplasm may be 



26 ESTIYO - AUTUMNAL MALARIA 

observed small vacuoles. Another degenerative change is less 
common and consists of the breaking up of the crescent into small 
fragments, known as fragmentation. At one time this was con- 
sidered a reproductive phenomena, but in the light of our present 
knowledge it is undoubtedly degenerative. Along with the cres- 
cents in the blood may be seen sometimes forms known as fusiform 
bodies, and they differ from the crescents only in that they are not 
crescentic in shape. The ends of the spindle are generally pointed, 
and the contained pigment, which is motionless, is often dis- 
tributed throughout the protoplasm. Marchiafava claims that 
these forms are most often found in pernicious cases of the 
disease. 

The Ovoid and Round, or Preflagellate Bodies.— Occur- 
ring in the blood with the crescents are often found ovoid or 
round bodies. These bodies are developed from the crescents, 
and this development can often be followed in the blood, a cres- 
cent changing into an ovoid body and that into a round or pre- 
flagellate organism. The ovoid bodies are really intracellular, 
and become extracellular prior to flagellation. 

The Flagellate Bodies.— Ever since the discovery of the 
Plasmodium of malaria by Laveran the nature and significance of 
the flagellated organism have constituted a mooted question. Held 
by some authorities to be of a degenerative nature, and by others 
as evidences of vital activity, the flagella have been closely studied, 
and a considerable literature has been accumulated concerning 
them. In the light of recent research, it can no longer be doubted 
that the evolution of the flagellated organism is a vital and most 
important phase in the life -history of the Plasmodium, and that 
the theory that it is a degenerative body must be abandoned. 

As a result of studies of the flagellated parasites, I believe 
that in the blood of patients suffering from the estivo- autumnal 
fevers there occur two forms of flagellated organisms: one a 
true flagellated parasite, the other a pseudo- flagellated parasite. 
To the first I have, for convenience, applied the term "active flagel- 
lated Plasmodium;" to the latter, "passive flagellated Plasmodium." 

Method of Obtaining Flagellated Organisms. — It is a well- 
known fact that under ordinary circumstances flagellated Plas- 
modia do not appear in a specimen of blood until some time after 
it has been removed from the body, generally from fifteen to 
twenty minutes. This rule has exceptions, however, for I have 
seen flagellated organisms in a blood specimen which had been 



THE FLAGELLATE BODIES 27 

removed only ten minutes from the circulation ; this is a rare 
exception and even in specimens long removed from the body 
flagellated parasites are not always found. I have found the 
following method of obtaining these bodies at once simple and 
effective. The finger or ear is carefully cleansed with alcohol, as 
are also the slides and cover -glasses. A small elastic band is 
now placed around the finger, or, if the lobe of the ear is used, 
it is compressed by an assistant. The puncture is made with a 
sterile needle or lancet and the first drop of blood wiped away. 
A second drop is now squeezed out and allowed to remain ex- 
posed to the air until the slide is breathed gently upon by the 
operator, when the tip of the drop of blood is gently pressed 
upon the surface of the slide which has been breathed upon. 
The cover -glass is then immediately placed over it, and the 
preparation is ready to examine. The slight exposure to the 
air, and the small amount of moisture upon the slide caused by 
breathing upon it, seems to hasten exflagellation, for specimens 
so prepared almost invariably contain flagellated bodies. In speci- 
mens prepared in this way I have noticed as many as twenty 
flagellated bodies in one preparation, and have often observed 
two in a single field. In my observations upon the bodies in 
question I have used this method exclusively, and have never 
experienced any difficulty whatever in finding material, — i. e., 
flagellated bodies for study. This method was first described, in 
part, by Manson. 

.Description of Flagellated Forms. — As I have stated, in cases 
of estivo- autumnal fever, I have almost invariably observed two 
seemingly distinct forms of the flagellated bodies. By this state- 
ment it is not meant that every case of estivo - autumnal fever 
examined showed these forms, but that the cases showing flagel- 
lated bodies presented them. 

Description of the Active Flagellated Plasmodium {Estivo -Au- 
tumnal Fever). — In examining a specimen of blood from estivo- 
autumnal fever, a number, sometimes only one or two, of rather 
large, almost circular, bodies are noted, with the characteristic 
pigment distributed over the surface and in very active motion. 
The motion is aptly described as dancing, is very much more 
rapid than that ordinarily present in the parasite, and at once 
attracts attention for that reason. Quite often, however, these 
swollen bodies will be seen, the pigment when first noticed being 
immotile, but suddenly developing very active motility while 



28 ESTIVO- AUTUMNAL MALARIA 

being observed. When the pigment is imrnotile it seems to be 
collected in small blotches or spots within the protoplasm of the 
parasite, but when in motion it is distributed quite evenly 
throughout the protoplasm. Besides the very active motion of 
the pigment -granules, if the edge of the parasite be carefully 
watched, it will be seen that it also is in motion, undulating 
and protruding, as though, as Richard said, something contained 
within the parasite were trying to escape. In a variable length 
of time — from five minutes to half an hour or more — the pigment 
will be seen to collect more centrally, the motility being some- 
what lessened, and instantly, like an explosion, there appear at 
certain portions of the edge of the parasite long, thin, color- 
less, actively moving filaments, which undulate rapidly, lashing 
about among the red corpuscles, to which they impart sometimes 
a peculiar spinning motion. The filaments may number from 
one to five, and are usually long and thin, having a slightly 
clubbed extremity. The junction of the flagellum with the para- 
site is not visible, it seeming to be continuous with the periphery 
of the organism. 

Besides the clubbed extremity, the flagella sometimes show 
small nodular swellings in their course, and also a few grains of 
pigment, which may be distributed along them or collected at 
the extremity. They generally measure about two or three 
times the diameter of the parasite from which they spring, but 
sometimes may be even longer. There also occur shorter, stouter 
forms, having a more sluggish, serpentine motion. 

There may now occur one of several things: either the flagella 
may break loose from the parent parasite, they may become 
gradually motionless and disappear, they may fold themselves 
around the parasite, which shrinks and degenerates, or the para- 
site may itself fragment and the flagella degenerate and disappear. 

In the first case, after the flagellum has lashed about among 
the blood -corpuscles for a variable length of time, seemingly 
trying to free itself from the mother parasite, it at last succeeds, 
and swims off in a serpentine manner among the red corpuscles. 
In some cases the flagellum tugs very vigorously in its efforts 
to free itself, actually pulling the mother parasite about but, of 
course, for only a minute distance. After it has become free it 
may exhibit motion for a long time, even an hour or more. If 
it chances that the flagellum was the only one given off from 
the mother parasite, the pigment of the latter becomes motion- 



CHANGE FROM CRESCENT TO FLAGELLATE 29 

less, the parasite quickly shrinks, and soon only a mass of 
pigment and degenerated material remains. 

In the second case, after persisting for some time, from half 
an hour to an hour or more, the flagella gradually become 
motionless and disappear, while the pigment ceases moving and 
the body of the parasite shrinks, becomes vacuolated, and soon 
presents a mere clump of debris. 

In the third case, after a certain time, the flagella become 
less actively motile and appear to become entangled with the 
body of the parasite, thus seeming to be folded about it, some- 
times loops being formed by the attachment of a flagellum to 
the mother parasite. The pigment in the body of the parasite 
becomes motionless and the same degenerative changes occur as 
in the former case. 

In the last case the parent parasite, either after the escape 
of one or more flagella or in cases where no escape takes place, 
breaks up into two or more parts, each part containing pigment, 
which remains in active motion for some time. On careful 
observation it will be seen that the fragments are united by 
very delicate hyalin threads. The flagella soon lose their 
motility and disappear, but the fragments containing the pig- 
ment may persist for a long while. ., In one case the pigment was 
seen to be in active motion in one of the fragments of such a 
parasite after a period of eight hours, at a room temperature 
of 70° F. 

It is not often that one has the good fortune to witness tne 
development of the crescent into t'a flagellated organism, and 
the following observation is therefore of importance. In observ- 
ing a sample of blood from a case of estivo- autumnal fever, 
which was particularly rich in crescents, I observed a medium - 
sized crescent entirely enclosed within a red corpuscle, occupying 
about one -half of it. While under observation, the crescent 
suddenly seemed to expand into a round body, the pigment, mo- 
tionless, occupying the center. After about ten minutes this 
round body suddenly became free, the red corpuscle seemed to 
melt away from around it, remaining as a pale shell close to the 
now free round body. Within a short time, probably about five 
minutes, the pigment within the round body became motile, at 
first slowly, then very rapidly, distributed throughout the proto- 
plasm of the organism, and suddenly two flagella shot forth from 
opposite sides of the parasite. One of these afterwards became 



30 ESTIVO- AUTUMNAL MALABIA 

detached and was lost sight of; the other, after persisting for 
about half an hour, ceased moving, and it and the body of the 
parasite became shrunken and degenerated. This observation con- 
clusively proves two things: (1) that the crescents are developed 
within the red blood -corpuscles, and (2) that the active flagel- 
lated parasite is developed from the crescents. It will be noticed 
that in the above observation it was the active flagellated parasite 
which was developed, and not the passive form, which will now 
be described. 

The Passive Flagellated Parasite (Estivo - Autumnal) . — In the 
blood of those cases of estivo- autumnal fever containing cres- 
cents there will be noticed numerous round and oval bodies in 
which the pigment is arranged in a wreath -like form. These 
bodies seem to be of two kinds : First and most numerous are 
those in which the pigment is of rather dot -like or rod -like 
form, and fine, sometimes motile and sometimes not, and those, 
fewer in number, and almost always round, in which the pigment 
is arranged in large black or dark brown dots, in a perfect circle 
and almost never motile. From the first variety arises quite often 
the active flagellated organism. 

The last-named round bodies merit a more minute description. 
They are clear-cut and definite, perfectly circular, and appear to 
possess a somewhat granular protoplasm; the pigment is arranged 
in round, very dark dots, forming a perfect circle, which may, 
however, be situated to one or the other side of the protoplasm 
of the organism. The pigment is generally non- motile, although 
occasionally a peculiar trembling motion may be observed; but 
the pigment retains its circular arrangement always, unless de- 
generative changes occur. 

No matter how long such a round form is watched, it will 
never be seen to present the phenomena of exflagellation. The 
pigment does not become active and distributed throughout the 
protoplasm, nor do flagella emerge from within it; but in exam- 
ining blood containing these bodies some of them are seen to 
possess one, two, or more flagella. These flagella are somewhat 
peculiar; they seldom possess a clubbed outer extremity, as is 
the case with the active flagellated body; but at their juncture 
with the round body a nodule is often noticed which resembles 
exactly the clubbed extremity of the flagellum of the active 
flagellated body. The movements, also, of these flagella are 
peculiar. Instead of the rapid serpentine lashings seen in the 



PLATE I 

THE QUOTIDIAN AND TERTIAN ESTIVO-AUTUMNAL PARASITES 

(The figures should be read from left to right) 

The Quotidian Parasite. Figs. 1 to 29. 

Figs. 1 to 7. King-forms of the Quotidian Parasite. 

Figs. 8 to 10. Pigmented forms of the Quotidian Parasite. 

Fig. 11. One ring-form and one pigmented form. 

Figs. 12 to 14. Pigmented forms of the Quotidian Parasite. 

Fig. 15. Intraeorpuseular segmenting form. 

Fig. 16. Intraeorpuseular ereseentic form. 

Figs. 17 to 20. Pigmented forms. 

Figs. 21 to 26. Crescentic forms of the Quotidian Parasite. 

Figs. 27 and 29. Flagellated forms of the Quotidian Parasite. 

Fig. 28. Preflagellate passive form of the Quotidian Parasite. 
The Tertian Parasite. 

Figs. 1 to 5. Hyalin forms of the Tertian Parasites. 

Figs. 6 to 16. Pigmented forms of the Tertian Parasites. 

Fig. 17. Intraeorpuseular ereseentic Tertian Parasite. 

Fig. 18. Intraeorpuseular segmenting Tertian Parasite. 

Figs. 19 and 21. Large pigmented forms of Tertian Estivo- autumnal 
Parasite. 

Fig. 20. Intraeorpuseular ovoid form of Tertian Estivo -autumnal Parasite. 

Fig. 22. Extracorpuscular segmenting form of Tertian Estivo -autumnal 
Parasite. 

Figs. 23 to 27. Crescentic forms of Tertian Estivo -autumnal Parasite. 

Fig. 28. Flagellated form of Tertian Estivo-autumnal Parasite. 



Craig. 



Plate I. 



• 


• © * e # 

2. 3. 4. 5- 6 - 


9 

7 


• » # # 

8. 9- 10- 11< 12. 


fc 


* © S fe © 


13. 

T 


14. 15. 16. 17 IS. 

13* C§7 6^ / /g) 


23. 


V — -^ ^ /-' 29. 
24. 25. 26 - <4 




The Quotidian Estivoautumnal Parasite, 



9 Q Q & O & 

• # # • # $ 

Q © a $ # 

13. 14 _ 15 

19. 20. ° ^r; 

22. 25 - 

o ^ ^ ^ 



Tertian Estivoautumnal Parasite, 




SIGNIFICATION OF VARIED FORMS 31 

flagella, as put forth from the active parasite, the movements are 
of a different character. The flagella seem to straighten and 
then relax, revolving apparently very rapidly upon their axes; 
sometimes they may be seen to pull themselves loose from the 
round body and again become attached to it. In the meanwhile 
the pigment within the round parasite has maintained its cir- 
cular arrangement, and is, at most, very slowly motile. 

Sometimes no nodular swelling is noted at the point of at- 
tachment of the flagella, and in such parasites the pigment has 
a more rapid vibratory motion. 

This same form occurs in tertian fever, but is larger, the 
pigment is less regularly arranged, and it is very much more rare. 

The question arises: What do these forms of the malarial 
parasite signify? A few months ago, in a conversation with 
Dr. Thayer, he mentioned their occurrence, which I had noted 
but had not paid much attention to. Since that time I have 
convinced myself that these forms occur, not as a rarity but 
very often, and that they represent, as has been suggested by 
McCallum, the efforts of flagella, which have been set free in 
the circulation, to penetrate within the interior of a parasite, 
represented by the round bodies just described. While I have 
not been so fortunate as have McCallum, Thayer and others, as 
to have actually seen the disappearance of a flagellum within 
one of these parasites, I am convinced from what I consider 
sufficient evidence to prove the fact, that this does occur. From 
the appearance and character of the motion of the flagella, and 
the passive condition of the organism to which they are attached, 
it seems to be impossible to believe other than that these flagella 
are striving to push their way into the parasite, and the fact 
that flagella have been seen to become detached from the par- 
asite and again attach themselves to it, is almost conclusive 
proof that such is the case. 

The circle of events is then, I believe, as follows: The active 
flagellated organism is developed from the crescentie estivo- 
autumnal organism. Flagella are produced and liberated, the 
mother organism, her duty fulfilled, degenerating and perishing. 
The free flagella swim actively about among the blood -corpuscles 
until they come in contact with the peculiar, round, passive para- 
site, which they endeavor to penetrate. McCallum and Thayer 
have seen this penetration occur, one of the flagella becoming 
submerged, so to speak, within the substance of the parasite. 



32, ESTIVO- AUTUMNAL MALARIA 

The nature of the process we are as yet ignorant of, but these 
two varieties of flagellated parasites do occur in the blood of 
malarial fever, and the observations upon them so far conclusively 
prove that the flagellate body is not a degenerative body, but is 
without doubt a very highly developed vital form of the Plas- 
modium of malaria. It is but reasonable to suppose that these 
forms are calculated to preserve the life of the parasite outside of 
the human economy, as they arise only when the blood has been 
exposed to external conditions, and that we have in this process 
another proof of the extra -corporeal existence, in another form, of 
the malarial parasite. 

The Origin, Nature and Significance of the Crescentic, Ovoid 
and Flagellate Bodies. — The crescents originate from young estivo- 
autumnal parasites, and their development has been carefully 
studied by Marchiafava and Bignami,* who say: "The young 
parasitic forms from which the crescents originate are distin- 
guishable from other forms of this species of parasite even when 
they are less than a quarter of the size of a red blood -cell. 
They occur as small round, ovoid or spindle-shaped bodies, which, 
when seen in a fresh specimen, appear to be quite homogeneous 
and to contain a greater amount of black pigment than do the 
bodies of equal size of the preceding cycle; the pigment, how- 
ever, is in the form of little rods, or somewhat larger granules, 
and is either irregularly disseminated in the body of the parasite 
or collected chiefly toward the periphery. These forms are not 
motile, they always occupy the lateral portion of the red cor- 
puscle, and in their development always tend to adapt their 
convex surface to the edge of the corpuscle itself. As the de- 
velopment proceeds even the bodies, which were originally round, 
tend to take on a long ovoid or rather spindle -form, as long as 
the distance between the poles of the ovoid does not exceed the 
diameter of the red corpuscle; where it does, the body either 
keeps the same shape or it becomes curved and forms the true 
crescent." 

It is very seldom that these young developing crescents are 
found in the peripheral blood, but blood from the spleen, and 
especially the bone -marrow, will show numbers of them; and it 
is generally believed that the bone -marrow is the point of origin 
of the crescents. 

As has been already shown, the ovoid bodies develop from 

*" Malaria, Twentieth Century Practice," Vol. XIX, page 44. 



THEORIES OF OBSERVERS 33 

the crescents, and the preflagellate and flagellate bodies from 
the o voids. 

A volume could be written in considering the significance of 
the crescents, ovoids, and flagellate bodies, for the theories con- 
cerning them have been many and various. I shall consider here 
only the most important. 

Canalis, Antolissei, Grassi, Golgi, Feletti, and others hold or 
held that the crescents were reproductive organisms, and multi- 
plied within the human economy. 

Grassi and Sakharov believe that they are a distinct species 
of parasite. Bignami, Marchiafava, and Celli believe the crescents 
to be sterile forms of the parasites, and this theory, modified so 
as to mean that the crescents are sterile forms only for the hu- 
man life -cycle, is to-day regarded as the true one, and has the 
benefit of experimental evidence. Personally, I have never seen 
any evidence of segmentation or reproduction in crescents, and 
am convinced that they are forms which only undergo reproduc- 
tive changes when removed from the human body, and after 
reaching the intestine of the mosquito. 

As to the significance of the flagellate bodies, the theories 
have been even more diversified than in the case of the crescents. 
I have already referred to some of these theories. Laveran 
believed that the flagellated parasite was the completely devel- 
oped malarial parasite, and that no parasite reaches perfection 
until it became flagellated. Grassi and Feletti held that they 
were degenerate bodies, while Dock regarded them as "resting 
forms," which, under certain conditions, were capable of again 
reproducing the typical parasite. This idea has been- strikingly 
confirmed by the mosquito theory. 

Mannaberg inclined to the belief that they were forms in- 
tended to perpetuate the life of the parasite outside the body, 
and Thayer inclined to the same belief. 

Manson was one of the first to emphasize the hypothesis that 
the flagellate bodies were forms which began in man the life- 
cycle afterward completed in the mosquito, and by the labors of 
Ross, Marchiafava, Bignami, McCallum, and others, it has been 
proved beyond all doubt that the flagellated bodies are sexual 
forms which assist in the development of the parasitic form which 
completes its life -cycle within the mosquito. 

Simond was the first to claim that the flagella were sexual 
forms, and he arrived at this conclusion from a study of the life- 



34 . ESTIVO- AUTUMNAL MALARIA 

cycle in other sporozoa, and further study by Schaudiun, Sied- 
lecki, McCallum, and others have enlarged and verified the sexual 
theory. Thayer, Koch, Marchiafava, Bignami, and most other 
authorities have expressed their belief in this theory. Marchia- 
fava and Bignami say, regarding this : " Reasoning from analogy, 
therefore, it seems probable that the forms which pass from man 
to the mosquito are sexual forms, and that an act of fecundation 
initiates the new life -cycle in the middle intestine of the insect." 

I believe that the history of the development of the parasite is 
probably then as follows: 

From the crescents are developed the ovoid bodies, and from 
these the round or preflagellate bodies. Certain of these round 
bodies become flagellated (the active flagellated body), while others 
do not. The first are male elements, the second female. The 
flagella (male elements) become free and penetrate and are re- 
ceived into the non- flagellated bodies (passive flagellated bodies, 
female elements), fertilizing them, and thus the new life -cycle is 
commenced. These pheuomena occur in the middle intestine of 
some species of mosquito, and will be considered more fully in the 
succeeding chapter. 

This theory has now the benefit of a large amount of experi- 
mental evidence, and it may be said that from the structure of 
the flagellum alone it would be almost impossible to believe 
other than that the flagella are intended to continue the prop- 
agation of the malarial parasite, as it has been demonstrated 
that nuclear chromatin is present within them. When to this 
fact is added the penetration of the round bodies by the flagella, 
as witnessed by McCallum and Thayer, the evidence is certainly 
convincing. 



CHAPTER IV 

THE LIFE-CYCLE OF THE ESTIVO- AUTUMNAL PARASITES WITHIN 
THE MOSQUITO 

As far as is at present known, the malarial parasite only 
undergoes development within certain species of mosquito, i. e., 
the species belonging to the genus Anopheles. I am indebted 
to the works of Marchiafava and Bignami for a large part of 
the description of these mosquitoes, which follows: The mos- 
quitoes belonging to the genus Anopheles are divided into two 
classes: those with and those without spotted wings. Of the 
first, there are the Anopheles oifurcatus and Anopheles nigripes. 
They are all small dark insects, either brownish black or brownish 
yellow in color. 

Of the last variety, or Anopheles with spotted wings, there 
are the Anopheles claviger and Anopheles pictus. The Anopheles 
claviger has wings marked by four black spots, the remainder of 
the wings being brown or yellowish brown in color. 

The Anopheles nigripes has a blackish brown wing and yel- 
lowish spots along the margins. These spots are three in number, 
the center being the largest, and the posterior the smallest, while 
on the remaining portions of the wing there are from five to 
seven brownish spots. 

An easy way to distinguish the Anopheles was said to be by 
noticing the position which the insect assumes when resting 
upon an object. The body of the Anopheles is always vertical 
to the object lighted upon, while the body of the genus Gulex is 
horizontal. This assertion has been proved false, and they are 
most easily distinguished in the larval stage. 

Methods of Study. — Those who have studied the life -cycle 
of the malarial parasite within the mosquito have used mos- 
quitoes within a glass tube, open at one end. This end is 
placed in contact with the skin of the person experimented 
upon, and the insects allowed to bite. The mosquitoes are then 
placed in a suitable receptacle and kept in a room having a 
temperature of from 70° to 80° F. 

(35) 



36 ESTIVO- AUTUMNAL MALARIA 

The following directions regarding the preparation of the 
mosquito for study are taken from Marchiafava and Bignami's 
masterly article upon "Malaria" in Volume XIX of the "Twen- 
tieth Century Practice of Medicine." They say: "As the life- 
phases of the parasite are observed in the mid -intestine and the 
salivary glands, the preparation of these parts is of great 
importance." 

" To prepare the middle intestine, the mosquito is anaesthetized 
by ether or tobacco smoke, and then fixed upon a piece of colored 
glass by means of a needle passed through the thorax, with the 
back towards the glass; then with teazing needles we press lightly 
at about the third abdominal segment, and very gently push 
apart the two needles, making gentle traction. By this means 
we draw out the whole intestine; the anterior intestine is ruptured 
at the thoracic segment, the posterior intestine remains adherent 
to the last abdominal segments, which are detached from the 
others, and the middle intestine, the most important for our 
researches, remains free. All this takes place in a small drop 
of physiological salt solution or in a weak solution of 1 to 2 
per cent formalin. 

" To prepare the salivary glands we proceed as follows : 
Holding the thorax fixed, as described, we detach the head by 
slight traction with the needle, and thus sometimes succeed in 
extracting all the glandular tubes with their excretory ducts; if 
this does not occur we shall have to tear off the anterior half 
of the thoracic segment with two fine teazing needles. 

"Fresh preparations, obtained in this manner, are examined 
in the sodium chloride or the formalin solution." 

To obtain permanent stained specimens the mosquito is 
hardened in alcohol or bichloride, imbedded in paraffin and 
sectioned, the sections being stained with hemotoxylin or methy- 
lene blue. 

Historical. — The history of the discovery of the role played 
by the mosquito in malaria is one full of interest, but, is so ex- 
tensive that it can only be touched upon here. 

Nuttall * states that nearly two thousand years ago the Soman 
writers Varro, Vitruvius and Columella mentioned the idea that 
mosquitoes bore a causal relation to malaria. Nott, in 1848, 
referred to it, and King, in 1883, wrote an excellent plea in 
its favor. Laveran, Pheiffer, and Manson have advocated it in 

* " Centralblatt fur Baeteriologie," etc., Feb. 14-21-28 and March 18, 1899. 



DEVELOPMENT WITHIN THE MOSQUITO 37 

their writings. Bignami, in 1894, did some experimental work 
along this line, which resulted negatively. To Manson, of Eng- 
land, belongs the credit of re -awakening an interest in the 
subject, and in his Goulstonian lectures, in 1898, he formulated 
a hypothesis, which very largely has been proven true by later 
experimental workers. To Ross, Bignami, Daniels, Dionisi, Bas- 
tianelli, Grassi, and Marchiafava the world is indebted for the 
knowledge of a new etiological factor in the production of 
malaria, i. e., the mosquito; and it is not too much to hope 
that in time this knowledge will lead to the suppression of one 
of the greatest foes of humanity and civilization. 

The development of the crescentic malarial parasite has been 
studied in the tissues of the mosquito by Grassi, Bignami and Bas- 
tianelli and by Ross and Daniels. In the description which fol- 
lows I have quoted largely from Bignami, whose studies in this 
subject have been most extensive and excellent. 

The Development of the Crescentic Parasite within the Mosquito 
{Anopheles claviger) . — I have already considered the fertilization 
of certain of the crescents by the flagella. This process, evidently 
sexual, takes place within the middle intestine of the mosquito. 
The crescents are known, biologically, as gametes, the male 
elements or active flagellated bodies as micro -gametocytes, the 
flagella as micro -gametes, while the bodies which do not become 
flagellated, i. e., the passive bodies or female elements, are known 
as macro -gametes. 

If an Anopheles claviger, which has been allowed to suck the 
blood of a person suffering from estivo- autumnal fever, crescents 
being present, and kept in a vessel having a constant tempera- 
ture of 86° Fahr., be examined, the following phenomena will 
be noted : 

If the middle intestine be examined about forty hours after 
the insect has sucked the infected blood, the intestinal wall will 
be found to contain spindle-shaped bodies, identical in appear- 
ance with those observed in human blood, save that they are 
larger. Often similar bodies are observed, but more oval in con- 
tour. These bodies are pigmented, but the pigment instead of 
being in a clump or scattered, as is the case in the human body, 
is arranged around the periphery. The bodies alluded to are 
situated on the outer side of the epithelium and basement mem- 
brane of the intestine, between the adipose tissue and muscular 
wall of the intestine, that is, they are within the substance of 



38 ESTIVO- AUTUMNAL MALARIA 

the intestine. After the second day the developmental changes 
are more rapid and noticeable. I 

Examined on the third or fourth day it will be seen that 
these bodies have increased much in size, and the protoplasm is 
granular and reticular in appearance. The pigment is less in 
amount, while the entire parasite is enclosed within a well- 
defined capsule. 

On the fifth day the increase in size is astonishing, the par- 
asites increasing to 70, or even more, so that they project 
from the intestinal walls, like bots in a horse. Within them are 
numerous minute bodies which are nuclei, and peculiar shining 
bodies which resemble fat. The capsule is very distinct. 

On the seventh day the interior of the parasite contains an 
immense number of very delicate filaments, having thinned 
extremities, each containing at its center a small amount of 
nuclear chromatin. These filaments are about 14 mm. in length 
and arranged like rays about a central mass, which may contain 
some black pigment. The capsule is very distinct. These fila- 
ments are the sporozoites. If the intestine be examined at a 
later day than the seventh, it will be found that the capsule 
has ruptured, thus setting free the sporozoites, and the remains 
of the capsule will be seen surrounded by the liberated sporozoites. 

If now the tubules of the salivary glands be examined, they 
will be found often crowded with these liberated sporozoites, and 
it is at this time that in biting a man the mosquito inoculates 
the sporozoites, which, after undergoing certain changes as yet 
undetermined, and which take place during the period of incu- 
bation, become the hyalin, intracellular, estivo- autumnal parasite. 

Peculiar brown bodies are also found in the encapsulated 
parasite within the mosquito, which vary in size and shape, 
being rod -like and round, straight or curved, and are considered 
to be degenerative bodies. 

Summing up, then, our knowledge of the life -cycle of the 
estivo -autumnal malarial parasite, it would be as follows: 

Human Cycle — 

1. Sporozoite. 

2. Hyalin amoeboid body. 

3. Pigmented body. 

4. Segmenting body. 

5. Crescentic body. 



DIFFERENCES BETWEEN ANOPHELES AND CULEX 39 

Mosquito Cycle — 

1. Crescentic body (gametes). 

2. Round, passive, flagellate body (macro -gametes) . 

3. Round, active, flagellate body ( micro -gametocytes). 
,. 4. Encapsulated, cystic body. 

5. Sporozoites. 

The conclusive experimental evidence in regard to the inocu- 
lation of estivo- autumnal malarial fever by the mosquito will be 
considered in the chapter upon etiology. 

In distinguishing between mosquitoes of the genus Anopheles 
and those of the genus Culex, the following points are to be 
observed, during the stages of development of the insect: 

The Eggs. — The eggs of Culex are deposited in boat-shaped 
masses, containing from 200 to 400 eggs. Those of Anopheles 
are arranged loosely upon the surface of the water. 

Larval Stage. — The larva of Culex comes often to the surface 
of the water to breathe, and its position is at an angle of 45 de- 
grees to the surface, while the larva o'f Anopheles remains always 
at the surface of the water and lies parallel to it. They also 
differ markedly in their structure. 

Pupal Stage. — The Culex is much more perpendicular to the 
surface of the water than the Anopheles. 

Adult Stage. — The palpi in the female Anopheles are much 
longer than those of Culex. 

The position of Culex when quiet is angular, while that of 
Anopheles is horizontal. 

Howard and Thayer have determined that the A. quadri- 
maculatus found in this country is identical with the A. maculi 
pennis of Italy. 



CHAPTER V 

CULTIVATION AND INOCULATION EXPERIMENTS— PHAGOCYTOSIS 
CLASSIFICATION 

Cultivation. — It may be said with certainty that no one has 
been able, as yet, to cultivate the malarial parasite in artificial 
media outside the human body. 

Coronado,* a Spaniard, is the only investigator who has even 
claimed to have done so, and his experiments have been repeated 
by other observers, none of whom have been able to confirm his 
results. He claimed to have successfully cultivated the parasites 
in water, which was infected. Such water, together with mud 
from the bottom of the infected pool, when placed in test-tubes, 
gave, according to him, cultures of the parasites, and the entire 
cycle could be followed. As stated, no other observer has been 
able to confirm his results, and in the light of our present knowl- 
edge they are evidently erroneous. 

The estivo- autumnal parasites have been kept alive outside 
the human body for some days. Sakharovt was the first to per- 
form such experiments successfully, and he found that the para- 
sites were alive in blood obtained by leeches from the human 
subject after a week, provided the leeches were kept upon ice. 
The parasites underwent no reproductive changes, however. 
Bluiner was able to confirm these experiments. 

Hamburger and Mitchell have performed similar experiments, 
which, as quoted by Thayer,! were as follows: 

"Mr. Hamburger took the blood from a case of estivo- 
autumnal fever with quotidian paroxysms at a time when only 
small amoeboid and ring-shaped, non -pigmented hyalin bodies 
were present. During the next several days he was able to dis- 
tinguish a slight increase in size, with the accumulation, in 
nearly every organism, of a few small, motile pigment -granules. 
On the eighth day the organisms were distinctly visible, each 

*"Cronica Medici Suirurgica de la Habana," Nov., 1892. 
fJahresberieht," Reference in Baumgarten's, 1890. p. 444. 
J "Lectures on the Malarial Fevers," 1897, p. 27. 

(40) 



INOCULATION EXPERIMENTS 41 

with a small group of slightly motile granules in the middle or 
at some point on the periphery of the parasite. 

"Mr. Mitchell placed a leech upon an individual suffering with 
a combined estivo- autumnal and double tertian infection. The 
blood showed two groups of active tertian organisms and a few 
crescentic and ovoid forms. In the body of the leech the tertian 
organisms were to be made out for ten days. The pigment was 
active for four days, but no amoeboid movement was to be made 
out in the parasites. The crescentic and amoeboid bodies re- 
mained unchanged; no flagellate forms were observed." 

In the light of the recent experiments with mosquitoes, it is 
interesting to note that in the leech the crescents and ovoids 
underwent no further development, and the flagellated parasites 
were entirety absent. 

Inoculation Experiments.— Many observers have been suc- 
cessful in producing malarial fever by inoculating a healthy in- 
dividual with blood from one suffering from the disease. It 
would be unprofitable here to detail all the experiments which 
have been performed along this line. Suffice it to say that 
among those who have successfully produced the disease in this 
way, may be mentioned Gerhardt, Mariotti, Ciarrochi, Marchiafava, 
Celli, Gualdi, Antolisei, Angelini, Di-Mattei, Baccelli, Sakharov, 
Bignami, and Bastianelli. 

It has invariably been found, when such experiments have 
been carefully conducted, that the type of parasite inhabiting the 
blood injected is found again in the blood of the individual in- 
fected, and is followed by the clinical symptoms of that variety 
of malaria produced by the type of parasite injected. 

In other words, the subcutaneous inoculation of blood from a 
person suffering from tertian estivo -autumnal fever into a healthy 
individual is followed by the occurrence of tertian estivo -autumnal 
fever in that individual, and this fact proves conclusively that 
there are varieties of the malarial parasite, each capable, and 
capable only, of producing the characteristic clinical symptoms 
with which it is always associated. 

As these experiments are of great value and interest, I give in 
detail two in which the estivo - autumnal parasites were inoculated. 

The first, performed by Di-Mattei,* is of interest because two 
types of fever were produced at different times. The patient 
experimented upon had suffered from quartan malaria some time 

* Preliminary Note, "Riforma Medica," 1891. No. 121, p. 544. 



42 ESTIVO- AUTUMNAL MALARIA 

previously, and had recovered. He was inoculated with blood from 
a case of irregular fever, which showed onlj' crescents at the 
time of inoculation. About eight days after inoculation the 
patient's blood showed non- pigmented, hyalin parasites. No fever 
occurred until sixteen days after inoculation, and it was nine days 
after the onset of fever before crescents were found in the blood, 
or twenty -five days after inoculation. Di-Mattei followed this 
experiment by injecting into the same patient blood from a case 
of quartan malaria, and in fifteen days quartan fever appeared and 
quartan parasites were present in large numbers in the blood. 
The second experiment which I shall quote was performed by 
Sakharov* upon himself. He allowed leeches to suck the blood 
of a case of pernicious malaria, which was comatose, and whose 
blood contained immense numbers of hyalin, non -pigmented ring- 
forms of the estivo- autumnal parasite. The leeches were kept 
upon ice for four days, at the end of which time he injected 1 
cubic centimeter of blood from one of them into his arm. 

At the end of twelve days he had a malarial paroxysm, accom- 
panied by a chill, which was repeated upon the following day. 
An examination of his blood showed numerous typical non- 
pigmented "ring -forms" of the estivo -autumnal parasites. 

From the foregoing it will be seen that estivo -autumnal fever 
can be transmitted from man to man by inoculation. 

Phagocytosis. — In examining the blood of patients suffering 
from estivo -autumnal malarial fever, in almost every case it will 
be noticed that many of the white cells or leucocytes contain 
malarial pigment, portions of malarial parasites or even the whole 
parasite. These leucocytes are the so-called phagocytes which are 
always present in malarial blood at some time. 

These pigment -containing cells were noticed in the blood be- 
fore the parasite of malaria was discovered, and Laveran, Marchi- 
fava, Celli, Golgi, Metchnikoff, Bignami, Osier, Barker, Dock, 
and Thayer have all added to our knowledge concerning these 
cells. In the tertian and quartan fevers they were noticed to be 
most numerous during or just after the paroxysms, while in estivo- 
autumnal fever they occurred at less regular intervals. 

Two theories have been advanced regarding the phagocytes, 
one, advocated by Metchnikoff t and his followers, that phagocytosis 
in malaria is an active protective process, and is the cause of 

*"Cent. fur Baekt.," Feb. 5, 1894, XV. Nos. 5 and 6. 
tRussk. Med., 1887. No. 12, p. 207. 



PHAGOCYTIC CELLS 43 

spontaneous recovery; the other, advocated by Bastianelli, that it 
has but little to do with spontaneous recovery and that the facts 
are not sufficient to prove that the phagocyte is, as Metchnikoff 
believed, an active enemy of the malarial parasite. 

From my own observations I must admit that I have seen but 
little to prove Metchnikoff' s theory, and while I admit that an 
active phagocytosis is undoubtedly of benefit to the patient, in that 
a certain number of parasites are destroyed and much pigment 
and debris removed from the blood by them, I believe that it has 
little to do with spontaneous recovery from the disease. 

The Phagocytic Cells. — The phagocytes are the polymorpho- 
nuclear, and the large mononuclear leucocytes, especially the 
latter. The eosinophiles and lymphocytes are not phagocytic in 
their action, and when pigment is seen within them it is, without 
doubt, accidental. 

Although the leucocytes, as a whole, are decreased in number 
in malaria, it is true that the phagocytic varieties are relatively, 
as a rule, increased; and this fact is one of the strongest argu- 
ments in favor of Metchnikoff' s theory as applied to malaria. 

Besides the varieties of leucocytes mentioned, certain other 
cells are phagocytic in malaria. Among these are endothelial cells 
(rarely), the cells, of the splenic pulp — especially macrophages — 
and cells of the marrow of the bones. In cases of pernicious 
estivo - autumnal malaria, examination of all these cells show them 
crowded with pigment and parasites. This is especially true of 
the macrophages of the spleen. These immense cells, from ten to 
twenty times as large as small leucocytes, will be seen to contain 
great blocks of pigment, parasites in various stages of develop- 
ment, and even entire infected red corpuscles. 

The phagocytes undergo certain degenerative changes, and such 
cells are most numerous in the blood of pernicious cases. The 
degenerative changes are: vacuolization, fatty degeneration, and 
fragmentation of the nucleus. These changes are most common 
and marked in the large mononuclear cells or macrophages. 

Time of Occurrence of Phagocytosis. — In the intermittent fevers, 
quartan and tertian, phagocytosis is most marked during or 
directly after the paroxysm, and this is true, also, in cases of 
uncomplicated tertian and quotidian estivo -autumnal fever, during 
an acute attack. If, however, the disease has persisted for a long 
while, or there is a double infection, the cyclic appearance of the 
phagocytosis cannot be demonstrated without repeated observa- 



44 ESTIVO- AUTUMNAL MALARIA 

tions and most careful study, and often not even then. In per- 
nicious cases phagocytes are, as a rule, very numerous, especially 
the large mononuclear variety or macrophages. Quinine tends to 
increase phagocytosis, especially in pernicious cases. In many 
cases of severe estivo- autumnal infection an examination of the 
blood always shows a marked phagocytosis, and in such cases it is 
impossible to ascertain the cyclic occurrence of the process. This 
is no doubt due to the rapid multiplication of the parasites. 

Substances taken up by the Phagocytes. — In the estivo -autumnal 
malarial fevers the following are found within the phagocytes: 
first and most common, free pigment; second, flagellate organ- 
isms; third, shrunken and degenerated red cells, both with and 
without parasites (these occur wholly within macrophages); 
fourth, segmenting forms (common in blood from the spleen, 
etc.) ; fifth, crescentic and ovoid forms (very rarely). The amount 
of pigment which the phagocytes absorb is very great, and there 
can be no doubt that they are of vast use to the organism in 
taking from the small capillaries this pigment, which might so 
easily occlude them. 

There is no more remarkable or beautiful object lesson in all 
pathology than the engulfing of a flagellated malarial parasite by 
a phagocyte, as it is often observed under the microscope, and in 
no other disease is phagocytosis so well illustrated. 

Significance of Phagocytosis. — I have already considered the 
question of the relation of phagocytosis to spontaneous recovery, 
and have noted the fact that it is just as active in fatal cases as 
in those which recover, as a rule, even more active. The question 
now arises: Has phagocytosis, in the estivo -autumnal fevers, any 
prognostic import"? I answer unhesitatingly, yes. The greater 
the phagocytosis is in any given case of tertian or quotidian estivo- 
autumnal malarial fever, the more severe is the infection and the 
more grave the prognosis. Especially is this true if, in the cir- 
culating blood, are found numerous large mononuclear phagocytes 
or macrophages. From my own observations I am convinced that 
a marked phagocytosis in estivo -autumnal fever, far from being a 
favorable sign, is almost typical of a pernicious infection, and if 
no cyclical course can be traced after many examinations, is abso- 
lutely typical and should be the signal for the institution of the 
most energetic measures for the treatment of the disease. If 
neglected or treated improperly, such cases almost invariably 
terminate fatally. 



CLASSIFICATION 45 

Classification. — The great majority of zoologists place ma- 
larial parasites among the Sporozoa, and some place them among 
the Rhizopoda. 

Laveran proposed the name Oscillaria malaria for the para- 
sites. Marchiafava and Celli gave us the term Plasmodium ma- 
larice, which is to-day the name generally used in describing the 
parasites. I have already mentioned the objections to this name 
and will not further discuss it here. 

There are three classifications which are of interest, those of 
Labbe, Kruse, and Grassi and Feletti. 

Labbe's Classifications. — Labbe classes all the blood -parasites 
in the Sporozoa and divides them into two classes: Haemosporidia 
and Gymnosporidia, in the latter division placing the parasites 
of man, which he well names Hsemamceba Laverani. In this 
same division he places the Halteridium and Proteosoma of 
birds. 

Kruse's Classification. — Kruse considers the Sporozoa as di- 
vided into six orders, the blood parasites belonging to the order 
Haemosporidia. He subdivides the Hgemosporidia into four gen- 
era, as follows: 1, Hasrnogregarina (lizard, turtle); 2, Drepanid- 
ium (frog); 3, Hsemoproteus (birds), and 4, Plasmodium (man). 

Grassi and FeletWs Classification considers that the malarial 
parasites belong to the Sarcodina, and divides them into two 
genera, as follows: 1, Heemamoeba: H. malarias (quartan para- 
sites); H. vivax (tertian); H. praecox, and H. immaeulata (estivo- 
autumnal parasites); also parasites of birds; H. relicta; H. sub- 
prEecox; H. subimmaculata. 2, Laverania; L. malarise (crescent 
forms); L. ranarum (frog), and L. Danilewsky (birds). 

These classifications are chiefly of zoological interest, and, as 
yet, no one of them has been decided upon as undoubtedly cor- 
rect. 

Varieties op Estivo- autumnal Parasites. — In considering 
the subject of classification of the malarial parasites, the question 
arises, Are there different species or varieties of the estivo - 
autumnal parasites, and can these different species be recognized 
both morphologically and clinically ? In answer, I have already 
expressed my opinion that there are at least two distinct varieties 
of the estivo -autumnal parasites, which, after sufficient practice, 
can be easily recognized by the microscope, and which, if alone 
and uncomplicated, give rise to perfectly distinct and character- 
istic clinical signs. 



46 ESTIVO- AUTUMNAL MALARIA 

Marchiafava and Bignami, in differentiating the tertian and 
quotidian estivo - autumnal parasites, call attention to the follow- 
ing: 1. Duration of life-cycle — twenty-four hours in the quo- 
tidian, forty-eight hours in the tertian parasite. 2. Pigmentation, 
greater in the tertian, the pigment motile. 3. Size of parasite, 
greater in the tertian. 4. Amoeboid motion, more marked in 
tertian and longer preserved. 5. Relation of the various forms 
to the life -cycle. 

In my researches I have confirmed most of Marchiafava and 
Bignami's conclusions, and in the numerous cases of both vari- 
eties of estivo-autumnal fever studied, have, I believe, been able 
to trace marked differences in every developmental stage of the 
parasites. I have already referred to these differences but will 
recapitulate them here: 

1. The Hyalin Stage. — The tertian estivo-autumnal parasite is 
larger, more clearly cut and refractive, and has more sluggish 
amoeboid motion than the quotidian parasite; it has often a 
signet -ring shape, while the quotidian is perfectly round. Only 
one parasite is found, as a rule, in a corpuscle in tertian infec- 
tion, while in quotidian two or more are common. The infected 
corpuscle is less crenated and lighter in color when infected by 
the tertian parasite.* 

2. The Pigmented Stage. — The tertian parasite is larger, and 
pigmentation occurs while the "ring-form" is still retained; in 
the quotidian the ring-form is never pigmented; amoeboid mo- 
tion is present after pigmentation, while in the quotidian it is 
always lost before pigmentation occurs; the tertian parasite is 
more sharply defined, and the pigment, present in larger amount, 
is finer, and is motile, while in the quotidian the pigment is 
always motionless and consists of one or two coarse granules. 
Only one pigmented tertian parasite occurs in a corpuscle, while 
two or more quotidian parasites may be present in one corpuscle; 
the infected corpuscle is more crenated and brassy when infected 
by the quotidian parasite. 

3. The Segmenting Stage. — The number of segments is greater 
in the tertian, and the segments are more oval in outline and 
larger. Segmentation occurs outside the red corpuscle in the 
tertian estivo-autumnal parasite more often, while in the quo- 
tidian it occurs within the infected corpuscle. 

* In the very young forms the tertian parasite is not as sharply denned as is the quotidian, 
which often looks as though it had been cut into the infected corpuscle. 



CYCLE OF DEVELOPMENT 47 

4. The Crescent Stage. — The tertian crescents are longer and 
more narrow than the quotidian, are more deeply pigmented 
and have less often a double outline. The protoplasm of the 
tertian crescent is more refractive and granular in appearance. 

5. The Flagellate Stage. — In the tertian parasite both forms 
of flagellate bodies heretofore described are larger and more 
deeply pigmented than in the quotidian. 

6. The Cycle of Development. — Twenty-four hours complete 
the cycle of development within the human body, in the quo- 
tidian parasite; forty -eight hours in the tertian. 

When we add to these numerous morphological differences 
the typical clinical phenomena exhibited by these parasites, it 
must, I think, be admitted that there are at least two varieties 
of the estivo- autumnal malarial parasite, a tertian and a quo- 
tidian; and from my own observations I can arrive at no other 
conclusion. The clinical differences will be dealt with fully in 
the section devoted to the description of the symptoms of the 
various forms of the fever. 

It may be urged that the differences noted may be due to 
the special conditions of environment, or unusual factors affect- 
ing the health of the individual, etc., and while, of course, 
we are unable to prove that this may not be so, yet they are so 
constant and harmonious that it is impossible to believe that 
they are accidental, and until such theories can be proved I shall 
continue to believe that the estivo -autumnal malarial parasites 
are divided into at least two varieties, the quotidian and tertian 
parasites. 



CHAPTER VI 

EXAMINATION OF THE BLOOD — METHODS OF STAINING — THE 
STRUCTURE OF THE ESTIVO - AUTUMNAL PARASITES AS RE- 
VEALED BY STAINING 

Methods op Examining the Fresh Blood.— There is no 
one thing more essential to success in recognizing the estivo- 
autumnal parasites in the blood than practical experience in the 
appearance of normal blood and the blood of other pathological 
conditions. He who supposes that he has only to look into his 
microscope at a specimen of blood, from a case of remittent 
malarial fever, to find the parasite, without having had previous 
experience in blood- work, will invariably be disappointed, and 
will give up the search in disgust. Success might possibly at- 
tend the search of such a tyro in the case of the large, fully 
grown, ordinary tertian malarial parasite, but never when the 
minute hyalin ring forms of the estivo- autumnal are concerned. 
The first thing, then, is some practical experience in examining 
the blood in health and disease and an intelligent conception of 
what one expects to find. 

The first essential to success is a good microscope, having an 
Abbe condenser, a mechanical stage, and a first-class one -twelfth- 
inch oil -immersion lens. The latter is absolutely essential in 
examining the blood for estivo -autumnal parasites, and nothing 
less than such a lens should be thought of. 

The same may be said, perhaps in a lesser degree, of the me- 
chanical stage. It increases the chance of finding the organisms 
very greatly, and this fact, together with the infinitely greater 
ease of manipulation, is worth far more than the slight addi- 
tional cost of such a stage. 

To knowledge, experience and a good microscope should be 
added energy and a large store of patience, for often a half- 
hour's search will be rewarded by finding but one parasite, and 
sometimes will go unrewarded. 

The following procedure is recommended in obtaining fresh 
blood for examination. The lobe of the ear or the top of the 

(48) 



OBJECTS MISTAKEN FOB PABASITES 49 

finger may be used, the ear preferably. The ear-lobe or finger 
is washed with alcohol and wiped dry. A perfectly clean cover- 
glass and slide are at hand, and the slide slightly warmed by rub- 
bing it gently. This facilitates the spreading of the blood. The 
ear-lobe or finger is pierced with a lancet or surgical needle, and 
the first and second drops of blood wiped away; the cover -glass 
is then touched gently to the summit of the next blood -drop and 
placed carefully upon the slide. If the cover -glass is thin, and the 
drop of blood on the glass small, the blood will spread evenly 
and quickly. If it does not, very slight pressure upon the cover- 
glass will suffice to spread the blood and will do no harm. Upon 
examining the specimen, if it is found that the blood -cells are in 
clumps or rouleaux, it should be discarded and one obtained in 
which the corpuscles are spread singly over the field. The prepa- 
ration of the specimen should take as little time as possible, as 
exposure of the blood to the air crenates the red cells and injures 
the chance of finding the parasites, A little practice will enable 
one to secure suitable specimens for examinations very quickly. 
Fresh specimens of blood will keep for a considerable length of 
time at room temperature — for several hours — and I have re- 
peatedly found such specimens well enough preserved after twelve 
hours to distinguish the malarial parasites. If the cover- glass 
is sealed with vaseline the specimen will keep much longer. 

Objects Apt to be Mistaken for Estivo- Autumnal Par- 
asites.— There are certain degenerative changes present in the 
red corpuscle at times, both in health and disease, which re- 
semble the estivo-autumnal malarial parasites very, closely — so 
closely, sometimes, as to deceive practiced investigators. The 
chief are: crenations, retraction of hemoglobin, vacuoles, and 
certain areas devoid of hemoglobin. 

Crenations occur if the blood is exposed long to the atmos- 
phere, or if the slide or cover -glass is not clean, and are con- 
fusing to an inexperienced observer if looked down upon directly, 
as they appear like round, rather hyalin bodies within the red 
corpuscle. 

Retraction of hemoglobin is often observed at some point on 
the periphery of the red corpuscle, and consists of small semi- 
circular areas devoid of hemoglobin. 

Vacuoles. — There is no more deceiving object in the blood 
than a small vacuole within a red corpuscle. Sometimes, espe- 
cially if the border of the vacuole alters in shape, the resem- 



50 ESTIVO- AUTUMNAL MALARIA 

blance to the hyalin disk -form of the estivo- autumnal tertian 
parasite is very marked. I have time and again had such 
vacuoles shown to me for Plasmodia by experienced microscopists 
who had had but little practice with malarial blood. The greater 
refraction of the vacuole easily distinguishes it from a parasite. 

Areas without hemoglobin occur in the red cells in certain 
diseases, as typhoid, tuberculosis, pneumonia, etc., and vary in 
shape. They may be situated at any part of the corpuscle, and 
may be round, spindle-shaped, oval, or ring-shaped. Some of 
them, especially the oval- and spindle-shaped ones, contain a 
minute dot, near the center, which resembles pigment. While 
these bodies are deceiving to the inexperienced, the absence of 
amoeboid movements and the much greater degree of refraction 
should serve to differentiate them from the malarial parasites. 

Staining Methods.* — Where it is impossible, for any reason, 
to examine suspected blood in the fresh condition, reliance must 
be placed upon stained specimens for diagnostic purposes; but 
only then. When, however, we wish to study the structure of 
the parasite of malaria, stained preparations are most valuable, 
and it is from them that we have learned much of the finer 
morphological characteristics of the various organisms. 

There are many ways of staining the parasites of estivo - 
autumnal malarial fever; but a description of a few of the most 
useful is all that will be attempted here. The blood -smears are 
prepared by carefully cleaning the lobe of the ear, puncturing 
it with a sterile needle or lancet, touching a clean cover- glass 
to the resulting drop of blood, and placing another cover -glass 
over it. The two are then slid very gently and carefully apart, 
and the smear allowed to dry. Care should be used not to get 
too much blood upon the first cover- glass, and to use no pres- 
sure in sliding the glasses apart. After drying, the smears are 
allowed to harden in equal parts of alcohol and ether for half 
an hour, when they are ready to stain. The Plasmodia are 
stained by nearly all basic anilin dyes, but not by the acid dyes. 

For staining I use either Romanowsky's or Chenzinsky's 
method, the latter preferably. Romanowsky's method is as 
follows: Two solutions are used — solution No. 1, a saturated 
aqueous solution of methylene blue; solution No. 2, a 1 per 
cent watery solution of eosin. The methylene blue solution 

*A portion of this section is taken from an article by the author in the " Medical News " 
of November 3, 1900. 



BOMANOWSEY'S STAIN 51 

should be at least one week old. The staining solution is made 
fresh each time it is used, and consists of one part of the 
filtered methylene blue solution added to two parts of the eosin 
solution, and thoroughly mixed. The smears are placed face 
down upon this solution and are allowed to stain from one -half 
to three hours or more. The best results are obtained after 
about two and a half hours' staining. By this method, the red 
corpuscles are stained red by the eosin and the parasites a deep 
blue by the methylene blue. Romanowsky believed that the 
nuclear chromatin stained a violet color, but I had never, until 
recently, been able to confirm his observations. Although very 
beautiful stained specimens can be secured by this method, I 
much prefer the method of Chenzinsky, for the reason that it 
gives a more natural appearance. By Romanowsky 7 s method, 
and, in fact, by most methods, the coloring by eosin is very 
vivid, especially that of the red corpuscles; whereas, in Chen- 
zinsky' s method the red corpuscles are stained more dimly, 
appearing almost natural in color, while the parasites are stained 
a fine blue, fully as well as by any other method. 

Chenzinsky' s method is as follows: A concentrated alcoholic 
methylene blue solution, diluted one -half with water, is added 
to an equal amount of a one -half per cent solution of eosin in 
60 per cent alcohol. This solution is bottled and kept, and im- 
proves in staining qualities by age. The specimens are stained 
with this solution for five minutes, and then washed in water, 
dried, and mounted in Canada balsam. Much better specimens 
are obtained by staining for two hours or more, and I have 
secured very fine specimens by leaving the smears in the stain- 
ing solution over night. 

There are numerous other methods of staining the malarial 
parasites, but these are the most satisfactory and useful. 

A word as to the use of stained preparations for diagnostic 
purposes: I am aware that a few authorities are staining prepa- 
rations almost entirely for diagnosis, but I believe that it is a 
cumbersome and very unreliable practice. Where it is impos- 
sible to keep a specimen of blood fresh enough to look at under 
the microscope, the use of stained preparations is, of course, 
necessary; but where it is possible to examine the blood fresh, it 
is always to be preferred, as it is infinitely more exact and sat- 
isfactory. I have seen many cases where the fresh blood showed 
numerous ring -forms of the estivo- autumnal parasites, in which 



52 ESTIVO - AUTUMNAL MALARIA 

smears taken at the same time and stained most carefully showed 
either none, or at most a very few dimly -colored parasites. There 
is also the danger of mistaking stained granular matter or debris 
lying upon the corpuscles for the small estivo- autumnal parasites 
in the smears, and this mistake can be very easily made by one 
who is unaccustomed to examining such preparations. The only 
strictly scientific way of diagnosing the various forms of the ma- 
larial parasites is by the microscopical examination of the fresh 
blood, and after all most specimens of blood will keep in a suit- 
able condition for examination, under ordinary circumstances, 
for six, eight, or even a greater number of hours. 

Before considering the staining reactions of the Plasmodia, 
a brief note as to the recent staining method devised by Futcher. 
It is to be recommended wherever speed in staining is desirable, 
where the fresh blood cannot be examined and a speedy diagnosis 
is essential. It is as follows: The smears are hardened in a 
1 per cent solution of formalin in 90 per cent alcohol for from 
a half to one minute. They are then dried and stained for from 
twenty to thirty seconds in the following solution of thionin, 
known as Marchand's: 

Saturated solution of thionin, in 50 per cent alcohol . . 20 
Two per cent solution of carbolic acid 100 

The solution should stand several days before using. After 
staining, the specimen is washed in water, dried, and mounted 
in Canada balsam. The red corpuscles are stained a very slight 
greenish hue, while the parasites are deep violet in color. Care 
should be taken not to stain for too long a time, and not to 
allow the formalin solution to act long, as it seems to cause a 
degeneration and vacuolization of. the red cells. The method 
stains the estivo -autumnal rings very satisfactorily. 

Laveran * has very recently devised a staining method which is 
a most excellent one, although I prefer either Romanowsky's or 
Chenzinsky's method. It is as follows: Three staining solutions 
are employed. 

Solution No. 1: Silver oxide methylene blue (Borrel blue) is 
mixed with 150 cubic centimeters of distilled water in a flask. 
Enough of the crystals are used to form a nearly saturated solu- 
tion. When the crystals are dissolved, the flask is filled with a 
solution of soda, and shaken, which causes a black precipitate of 

*"Comptes Rendus, Soc. de Biologie," June 9, 1900. 



STRUCTURE OF ESTIVO - AUTUMNAL PARASITES 53 

silver oxide to be deposited. This is washed carefully, and an 
aqueous saturated solution of medicinal methylene blue is poured 
over it, and allowed to stand for eight days, shaking occasionally. 

Solution No. 2 : An aqueous solution of eosin, 1 part to 1,000. 

Solution No. 3 : A 5 per cent aqueous solution of tannin. 

The stain is prepared just before using as follows: 

Solution No. 1 1 c.c. 

Solution No. 2 4 c.c. 

Distilled water 6 c.c. 

Each should be filtered before mixing. 

The blood -smears are fixed with alcohol for twenty minutes. 
Five to ten minutes' staining will suffice to stain the parasites. 
When stained, the specimen is rinsed and treated with the tannin 
(Solution No. 3) for a minute, then washed and dried. The stain 
is very delicate and reliable, staining the nuclei of the cells a deep 
violet, the red corpuscles a pink, the protoplasm of the parasites 
a pale blue, and the chromatin a violet -red. 

I have had but little experience with this stain, but it is no 
doubt an excellent one, provided it is prepared and executed as 
described by Laveran. 

The Structure of the Estivo -autumnal Parasites as 
Revealed by Staining. — The following observations upon the 
staining reactions of the estivo -autumnal parasites are the result 
of experience gained from the examination of large numbers of 
stained specimens, and data from the writings of other observers. 

1. Staining Reactions of the Ring-Forms of the Estivo-autumnal 
Parasites. — The staining reactions are alike both for the quotidian 
and tertian estivo -autumnal parasites. 

The stained rings present the following appearance: A more 
or less deeply stained, thin ring, encircling a round portion the 
color of the corpuscle. At some portion of the stained ring 
there may often be seen a granule or dot of chromatin stained a 
dark purplish red which may be situated at the- edge of the ring, 
projecting into the central unstained portion. In fact, at this 
stage, the parasite consists of an outer deeply stained portion, 
the protoplasm of the organism; a very rudimental nucleus, rep- 
resented by the deeply stained chromatin granule or granules, 
situated somewhere upon the inner periphery of the stained por- 
tion, and an inner round or oval unstained area, representing a 
nutritive vacuole; sometimes the chromatin is situated within this 



54 ESTIVO- AUTUMNAL MALARIA 

unstained portion and separated from the stained portion of the 
parasite. 

In the pigmented rings there is a deeply stained outer portion 
(the ring), in which are situated the pigment -granules, generally 
at the periphery; the deeply stained violet chromatin is larger and 
generally situated within the colored ring, and may be surrounded 
by a pale area. 

2. Staining Reactions of the Pigmented Disk -Form. — As the 
parasites become larger, the ring-form is lost, and the following 
appearances are present in stained specimens: The entire parasite 
is colored blue, most intense in the outer portion and gradually 
fading as the center is approached. At or near the center may 
sometimes be seen a deep reddish violet or almost black dot or 
spot, evidently chromatin, surrounded by a pale, almost unstained 
area. The nearer the parasite is to segmentation, the less does 
the chromatin show, until just before segmentation, when it again 
becomes visible in rare instances. 

Marchiafava and Bignami* claim that with Romano wsky's stain 
the chromatin -granules can always be differentiated, and they 
thus describe the staining reactions of the more fully developed 
parasites: "By this method, indeed, we find that some of the 
bodies with blocks of pigment [usually the smallest] are com- 
posed of a peripheral portion stained blue [protoplasm] , and of 
a central or sub-central formed of granules or filaments stained 
red [chromatin] , surrounded by a pale substance which remains 
almost or altogether unstained [nuclear juice] . By the sides of 
these are seen other bodies with pigment [usually larger than 
the preceding], in which are two or three clumps of chromatin, 
each one surrounded by a zone of pale substance. Thus by a 
successive series of division of the nuclear protoplasm we have 
the formation of a varying number of little round or oval bodies 
of chromatin which are readily stained and are compact in 
appearance, that is to say, without recognizable structure and 
apparently homogeneous. At this point occurs the division of 
the body with the block of pigment into daughter bodies." 

3. Staining Reactions of the Segments. — Each segment or 
spore, when stained, is seen to consist of a round or oval pale 
blue mass of protoplasm, containing a minute, deep reddish 
violet granule of chromatin. 

As the parasite develops, the chromatin increases gradually 

*" Malaria," 1900, p. 39. 



STAINING REACTIONS OF CRESCENTS 55 

in amount, and tends to become arranged in granules or strings 
which are often very thickly packed together. 

4. Staining Reactions of the Crescents and Ovoids. — The 
crescents and ovoids are seen, when stained by Romanowsky's 
method, to consist essentially of a central dimly stained vesicle, 
containing deeply stained reddish chromatin granules, surrounded 
or even invaded by rodlets and grains of pigment, which are in 
turn surrounded by the protoplasm of the crescent, which stains 
a beautiful blue. Surrounding the crescent is often seen a red- 
dish-stained border, constituting the membrane of some au- 
thorities, but which is in reality the remains of the red blood- 
corpuscles which has become folded about the organism. This 
is the explanation, also, of the double outline so often seen 
around crescents, such an appearance being due to the retrac- 
tion of the hemoglobin about the body of the parasite, which 
stains with eosin. The discovery that chromatin exists in the 
crescents does away entirely with the arguments of those ob- 
servers who have regarded them as sterile bodies, incapable of 
further development under any condition. 

The crescent -forms of the estivo- autumnal parasites present 
many interesting staining phenomena. In those crescents in 
which the pigment is collected near the center, the organism, as 
a whole, takes a rather dim blue color, the poles staining much 
more deeply, while the center, in which the pigment lies, is often 
unstained or but dimly stained (vesicular nucleus). At each 
pole, as a rule, may be seen a very deeply stained semi -lunar 
area extending to its periphery and covering the horns of the 
crescent. The appearance presented is that which would result 
had each horn of the crescent been dipped into a darker staining 
fluid and withdrawn. Between the deeply stained horns of the 
crescent, and lying within the more dimly stained protoplasm, 
are often seen very deeply stained round or oval spots irregularly 
distributed. In some crescents these deeply stained spots are 
very distinct, and occupy a large part of the protoplasm of the 
crescent. As a rule, the area in which the pigment lies, and 
immediately surrounding it, stains very faintly, or not at all, 
but it is not rare to see a darkly staining belt or band passing 
through the center of the crescent, seeming to divide it into two 
parts. This appearance, however, is not common and does not 
by any means prove the dual nature of the crescent. Surround- 
ing the crescent, in the majority of instances, is a narrow eosin- 



56 ESTIVO- AUTUMNAL MALARIA 

stained border, believed to be the remains of the red corpuscle 
in which the crescent was developed. This red -stained border 
does not always, however, entirely surround the crescent; some- 
times it is observed only between the two horns, forming the so- 
called "bib;" sometimes it is absent there and present over the 
convex portion of the crescent; sometimes it can only be seen 
covering the horns or one horn of the crescent. It is often 
observed to be broken or ragged in outline and interrupted in 
places, thus suggesting the gradual disintegration of the red 
cell. Crescents are often observed which do not show any eosin- 
stained border, and in such cases we may assume that the de- 
struction of the red cell is complete, and the crescent is free in 
the blood-plasma. 

While the above description applies to the majority of stained 
crescents, many exceptions occur. Quite often crescents are 
observed almost uniformly stained throughout; others do not pre- 
sent the deeply stained spots or polar staining; others stain very 
dimly at one end and deeply at the other. In fact, it would be 
almost impossible to describe all the variations which may occur, 
but in the vast majority of examinations of stained crescents 
the description given will be found correct. 

The ovoid bodies stain exactly as do the crescents, so far as 
I have been able to observe, save that the polar staining is not 
so pronounced. 

5. The Staining Reactions of the Flagellate Bodies. — It is 
exceedingly difficult to stain the flagellate bodies, but Marchia- 
fava, Bastianelli, - Bignami, Manson, Gotye and others have 
succeeded in doing so, and in stained specimens have found the 
structure of the flagellates to be as follows: The round body 
takes a blue stain and the chromatin is arranged about the 
periphery in small clumps. From these clumps or chromo- 
somes there are projected slender filaments of chromatin which 
occupy the center of a slender mass of protoplasm, derived 
from the protoplasm of the organism. This slender thread of 
chromatin enveloped in protoplasm constitutes the flagelluni. 
Some flagella do not possess any chromatin, and in some the 
chromatin seems to be irregularly distributed. 

Bastianelli* has demonstrated that in the free flagella the 
chromatin is collected at the center, the two extremities consist- 
ing of protoplasm. He is inclined to believe that the crescents 

*" Lancet," London, 1898. Vol. II, p. 1620. 



PLATE II 

STAINED INTRACORPUSCULAR AND CRESCENTIC FORMS 
OF TEE ESTIVO-AUTUMNAL PARASITES 

Note the polar staining of the crescents, the irregular staining 
of the protoplasm, and the eosin - stained border. Some of the 
crescents have lost the eosin -stained rim and stain almost uniformly 
throughout. 



Craig. 



Plate II. 



4 S & ^ f 



f 



~j&. 



n 



12. 13. 



14. 15. 



i> 




O 



26 



* 



# 



<J 



24. 25. 






27. 28. 29. 30 - 

^(!!^, Del. 

Stained forms of the Estivoautumnal Parasites. 



STAINING OF FLAGELLATE BODIES 57 

from which the flagellated bodies develop are sterile while they 
remain within the human body. The discovery of chromatin 
within the flagella of the malarial parasites adds another link to 
the conclusive evidence in favor of a life -cycle of the organism 
outside the human body, as it proves that they are living cells, 
and not, as was long believed, evidences of degeneration. 

Note. — Ewing, in a recent article ("Journal of Experimental 
Medicine," March 25, 1901, p. 433), speaks very highly of the 
Nocht-Romanowsky staining method. This method as described 
by Ewing is as follows: 

1. To 30 c.c. of polychrome methylene blue (Griibler) add five 
drops of a 3 per cent solution of acetic acid (U. S. P.. 33 per cent). 

2. Make a saturated (1 per cent) watery solution of methylene 
blue (Griibler), dissolving the dye by gentle heat. This solution 
should be at least one week old. 

3. Make a 1 per cent solution in water of Griibler aqueous 
eosin. 

The mixture is prepared as follows: 

To 10 c.c. of water, add 4 drops of the eosin solution, 6 drops 
of the polychrome methylene blue and 2 drops of the 1 per cent 
methylene blue, mixing well. The preparations are stained for 
two hours, specimen side down. The best results are obtained 
after twenty-four hours. 

Personally I have never used this method of staining, but it 
is undoubtedly a valuable one. 



CHAPTER VII 

ETIOLOGY— PREDISPOSING CAUSES, GENERAL AND LOCAL 

Predisposing Causes, General. — The direct cause of the 
estivo- autumnal or remittent malarial fevers are, as has been 
demonstrated, hcemamcebce, known as the Plasmodia of estivo- 
autumnal fever. These organisms are alone capable of exciting the 
disease, but there are certain conditions which favor the develop- 
ment of the parasites within the body or indirectly aid in infection. 

These are known as predisposing causes and will be briefly 
considered here. 

1. Locality. — A knowledge of the habitat of this form of 
malaria is most important, as localities which are known to be 
infected can thus be avoided and, also, because residence in a 
malarial district is a predisposing cause. While the intermittent 
malarial fevers are of world-wide distribution, the same cannot be 
said of the estivo-autumnal forms of the disease, which are 
much more limited in their distribution, and very uncommon in 
northern latitudes, becoming more and more common as we 
approach the tropics. 

In North America estivo-autumnal fever prevails along the 
low regions of the southern coast line, being very severe in the 
Gulf states. It is common and severe along the Mississippi and 
its southern branches. It is less frequently met with along the 
Pacific coast, and not further north than the northern coast 
region of California. It prevails along the Atlantic coast-line as 
far north as Delaware. In Cuba, along the coast, the most 
pernicious forms occur. 

In South America very severe types of the disease are com- 
mon, especially along the coast regions of Colombia, Venezuela, 
Guiana, Brazil, Ecuador, Peru and Chili. The whole Atlantic 
coast of Central America is a hotbed of estivo-autumnal fever, 
and here the very worst forms occur. 

In Europe, the shores of the Mediterranean, i. e., Greece, 
Crete, Italy, Venice, Sicily, France, Spain and Portugal, suffer 
from this type of malarial fever, and it is especially common 

(58) 



PREDISPOSING CAUSES 59 

and pernicious around the Roman Campagna and Pontine 
Marshes in Italy. It is also common along the Black and 
Caspian seas. 

In Asia: India, Ceylon, portions of China and Arabia, and 
the islands of the Malay archipelago are infected with the 
disease. Until recently the Philippines were not considered as 
being very malarious, but the number of our soldiers returning 
from there infected with estivo- autumnal fever has considerably 
changed the current opinion regarding these islands. 

In Africa are some of the most dangerous lurking places of 
this disease, the worst areas being those along the west coast, 
and along the Senegal, Congo and Niger rivers. Madagascar, 
Reunion and Mauritius islands present pernicious varieties of 
the disease. Around Delagoa bay and along the east coast of 
Africa estivo-autumnal fever is prevalent. Lower Egypt, the 
Soudan, the Nile delta, Tripoli, Tunis, and Algeria all harbor 
this disease. 

2. Climate. — If we look carefully over the areas of distribu- 
tion of estivo-autumnal fever, we perceive that it is most com- 
mon and pernicious in tropical countries. Heat, then, is an 
essential predisposing cause of estivo-autumnal fever. When it 
prevails in more northern or temperate latitudes this form of 
fever occurs chiefly during the summer and autumn months, 
while, on the contrary, in the tropics, it occurs throughout the 
year, save for slight differences due to the rainy and dry seasons. 

3. Time of Bay. — From the beginning of our knowledge con- 
cerning malaria it has been known that there is much greater 
danger of contracting malaria at night than during the day. In 
the light of our present knowledge that malaria is due to inocu- 
lation by the bite of the mosquito, this fact is strong confirma- 
tory evidence, were it needed, for it is during the night that the 
mosquitoes mostly bite. 

4. Altitude. — The lowlands along the coast and rivers of warm 
countries are the principal home of the estivo-autumnal fevers, 
while the mountains, or even slight elevations, are immune, or 
nearly so. That high altitudes are not always safe, however, is 
evidenced by the fact that in the Philippines, certain valleys are 
almost free from malaria, while the hills in the vicinity are no- 
toriously infected. People sleeping in the lower stories of houses 
are more apt to become infected with malaria than those in the 
upper stories. This fact was supposed to be due to certain low- 



60 ESTIVO - AUTUMNAL MALABIA 

lying noxious vapors from malarious regions penetrating the 
lower more often than the upper floors of dwellings. The fact 
is easily explained when we know that the mosquito seldom flies 
to any height. 

5. Moisture. — Marshes and damp regions are, as a rule, con- 
ducive to malaria, and moisture seems to be a most important 
factor in the distribution of the disease. Here again, the truth 
of the inoculation of the disease by mosquitoes is confirmed, for 
it is precisely in such places that mosquitoes are most numerous 
and breed most abundantly. 

6. Soil. — Tropical jungles, low marshy lands, or lands covered 
with pools of stagnant water, are most apt to be malarious. This 
is not due directly to the soil, but is, as Marchiafava well says, 
"due to the fact that beneath a more or less thick stratum of 
humus there is an impervious layer" which gives rise to pools 
of water and general moisture of the soil. Such a soil favors the 
spread of the disease, as it brings about favorable conditions for 
the development of the infecting mosquitoes. As Marchiafava 
and Bignami say: "These conditions consist in the formation in 
the summer ... of small collections of stagnant water covered 
with a. layer of vegetation, surrounded by mud and shaded by 
rank vegetation. Now, in these stagnant pools, the larvae and 
nyrnphas of the mosquitoes, which infest the house of the wretched 
sufferers from the fever, find a suitable rest." 

Turning up of the soil in places long undisturbed has often 
been followed by extensive outbreaks of malaria. 

7. Winds. — Some authorities have considered that malaria 
could be transmitted by the winds, while others have regarded 
winds as being protective in their nature. The latter theory is 
probably correct, for as malaria is inoculated by the bite of the 
mosquito and as these insects do not fly about when the wind is 
blowing, it follows that the malaria is not transported by the 
wind. 

8. Rain. — Rain favors the production of malaria because it 
favors the breeding of the mosquito. Added to this, rainy weather, 
by diminishing the resisting powers of the individual, favors the 
development of the disease in that individual after he has become 
infected by the mosquito. 

Rains favor the breeding of the mosquitoes by giving rise to 
shallow, stagnant pools, which form ideal depositories for the eggs 
of the insect. 



LOCAL AND OTHER FACTORS 61 

Local Predisposing Causes.— 1. Race.— According to Thayer 
and Hewetson, the negro is less liable to contract malaria than 
the white man. As newcomers to a malarial district are much 
more liable to infection than old residents, it may be that the 
apparent immunity of the negro is only, in fact, apparent, for 
it should be remembered that it is the dark-skinned races which 
chiefly inhabit the most malarious countries. 

2. Age. — Children are more susceptible to infection than 
adults. This is probably due, partly, as suggested by Marchia- 
fava, to the fact that mosquitoes bite children in preference to 
adults. 

3. Sex. — When equally exposed, both sexes have the same ratio 
of infection; but, as a matter of fact, malaria is more common 
in men than in women, as the latter remain at home more and 
are not exposed as often to the bites of the mosquitoes. 

4. Occupation. — The occupation of man becomes a predispos- 
ing factor in the production of the disease in proportion to the 
chances that occupation gives him of infection. Laborers work- 
ing at ditching, railway building, etc., which necessitate the 
turning up of the soil, are especially liable to attacks of malaria. 
An instance of this was the terrific mortality from estivo- 
autumnal fever during work upon the Panama canal. 

Other Predisposing Factors.— Anything which lessens the 
individual's resisting powers, such as sudden chilling, dissipa- 
tion, overeating, privations, overwork — mental or physical — etc., 
is a predisposing cause. 



CHAPTER VIII 

ETIOLOGY (CONTINUED) DIRECT INFECTION— BY AIR— BY WATER 
—BY INOCULATION 

The malarial poison may, according to various observers, 
reach the human economy through three channels: by the respir- 
atory tract, by the digestive tract, or through the skin by 
inoculation. The first two channels include the air and water 
theory of the transmission of the disease, and neither have 
sufficient experimental data to establish them. The last or 
inoculation theory is the only one which has been proved ex- 
perimentally and is worthy of acceptance. Before considering 
it in detail a short review will be given the air and water 
theories. 

1. Transmission by Air. — Until recently most authorities 
considered that malarial disease was transmitted by the air, 
which, in localities infected with malaria, carried the parasites, 
which were supposed to be present in the soil or water. Al- 
though accepted by many, this theory has never had a single 
experimental fact to uphold it. 

To this theory we owe the common opinion that the air of 
malarious localities is poisonous; that the vapors and fogs arising 
from marshes or low rich lands are laden with malaria, and nu- 
merous other fanciful opinions, which, even though we now know 
them to be false, it will take years to efface. 

It would seem that the most convincing argument against the 
transmission of malaria by the air is the fact that the disease is 
not conveyed by the wind, for it is impossible to suppose that if 
the malarial germ were present in the air it would not be carried 
by the winds. 

2. Transmission by Water. — Numerous facts have been 
brought forward by the believers in the theory that water trans- 
mits the malarial poison, but all of them can be otherwise ex- 
plained, and there is no experimental evidence to prove the truth 
of the theory. Large numbers of the experiments have been per- 
formed (all of which have ended in failure), to produce the dis- 

(62) 



INOCULATION BY MOSQUITO 63 

ease by drinking water from infected places. Celli and Zeri have 
investigated this subject very thoroughly, and have come to the 
conclusion that malaria is never transmitted by the water of 
marshes or swamps. Their experiments were very carefully per- 
formed, and failed utterly to indicate that malarial fever was due 
to the drinking of water from malarious districts. 

More recently Ross claims to have produced malaria in a 
human being by allowing him to drink water which contained the 
dead bodies of mosquitoes infected with the malarial parasite. 
He followed this supposedly successful attempt by others, but he 
was never afterward able to produce the disease; so that it is but 
reasonable to regard the first and successful attempt as merely a 
coincidence. It may be that malaria can be thus transmitted, 
but there certainly exists no valid reason to-day for such a 
belief. 

3. By Inoculation, Through the Skin, by the Mosquito. — 
This is the one method of infection which has been confirmed by 
abundant experimental evidence, and which, to-day, is accepted 
by all authorities, as the most common means of infection. 
Marchiafava and Bignami go even further and claim that the 
inoculation of malaria by the mosquito is the only way that the 
disease is transmitted. I believe, in the present rather dimly 
defined state of our knowledge, that such a statement is too 
radical, but am willing to admit that as far as we at present 
know, the theory of the inoculation of the disease by the mos- 
quito is the only one which is worthy of our belief. In a most 
convincing manner Marchiafava and Bignami * refute the argu- 
ments of the air and water theories, and sum up in favor of the 
inoculation theory as follows: "Thus, admitting that malaria in 
man is the result of inoculation by mosquitoes, it is not difficult 
to explain why it is practically not carried by the wind ; it is also 
easy to understand why the danger of acquiring malaria is great- 
est in the evening and the night. We see at once why the infec- 
tion does not rise far above the ground; we comprehend readily 
the danger of sleeping in malarious districts; and finally, this 
theory explains perfectly the well-known prophylactic efficacy of 
mosquito nets in regions where malaria prevails. Also this 
agrees with what we know of the habits of mosquitoes in malari- 
ous countries, which sting especially at evening and during the 
night, do not fly far from marshes, or places where the proper 

*•" Malaria: Twentieth Century Practice," Vol. XIX, p. 111. 



64 ESTIVO- AUTUMNAL MALARIA 

conditions of their existence prevail, are in hiding during the 
day out of the way of the winds, are most numerous in places 
where malaria prevails, disappear from places where works of 
sanitation have removed the conditions necessary to their exist- 
ence, do not fly to any great height above the ground," and many 
other arguments. 

Nuttall,* in an elaborate review of the evidence in favor of 
the transmission of malaria by the mosquito, mentions the fol- 
lowing facts, which I have tabulated below: 

1. The Malarial Season. 

a. Corresponds to a period of warmth and moisture, condi- 
tions most favorable for the development of mosquitoes. 

o. Develops after the first rains, which form pools in which 
mosquitoes multiply. 

c. Malaria often ceases after excessive rains, when such pools 
are flooded and washed out. 

d. Malaria is more prevalent in wet years, when mosquitoes 
are most numerous. 

2. The Malarial Country. 

a. Malaria is most common in low, moist countries, swamps, 
jungles, low seaboards, river deltas and valleys, and in such 
places mosquitoes most abound. 

o. Malaria is most common as the equator is approached, 
and insect-life is also most abundant throughout the year. 

3. Conditions Affording Protection from Malaria and Mosquitoes . 
a. Protection of the body, as closing the windows and doors 

at night and using mosquito nets, gauze veils, curtains, etc. 
This has long been recognized by the inhabitants of malarial 
countries. 

o. Thickly-built houses exclude malaria. Malarial fever sel- 
dom penetrates far into cities, as mosquitoes are stopped by 
walls, hedges, etc., and are attracted by the lights in the suburbs. 

c. Intervening woods and expanses of water protect from 
malaria, the woods by obstructing the passage of the mosquito, 
acting as a sort of screen. Bodies of water are protective be- 
cause the mosquitoes perish in them or do not try to cross 
them, as the mosquito is not capable of prolonged flight. 

d. Cultivation of the soil: Malaria is prevented by cultiva- 
tion of the soil, due to the fact that this destroys the stagnant 
pools and swamps, or "mosquito nurseries." 

* Johns Hopkins Hospital Reports, Vol. VIII. 



MALARIA AND MOSQUITOES 65 

e. Flooding the laud will prevent malaria by destroying the 
breeding -places of the mosquitoes. 

/. Avoidance of sleeping out-of-doors at night or exposure 
after sunset: Mosquitoes bite mostly at night, and when asleep 
the person bitten does not know it, and thus is bitten often. 

g. Use of fires: Fires indoors or out protect against malaria 
because the mosquitoes are attracted by them and fly into them 
and perish before reaching the person. 

h. Immunity of persons working in sulphur mines: Due to 
the fact that the mosquitoes are repelled by the smell of sulphur. 

4. Influence -of Occupation. — The more exposed a person is, 
by occupation, to night air in malarious districts or to the soil, 
the more liable is he to contract malaria, as he is thus exposed 
to the bites of mosquitoes. 

5. Effect of Turning up the Soil. — Malaria often follows ex 
cavations, etc., and it is probable that in such cases pools of 
water are formed in the excavated land, thus giving rise to fit 
breeding places for th& mosquito. 

6. Elevation and Malaria. — Malaria is most dangerous near 
the ground, and people living in the upper stories of houses 
escape. Mosquitoes fly low and the nearer the ground one is 
the more apt he is to be bitten. 

7. The Bole of Insects and Ticks in Other Hematozoal Dis- 
eases, as the mosquito in filariasis, the tick in Texas fever, etc. 
Reasoning from analogy this is presumptive evidence. 

8. The Coincidence of Malaria and Mosquitoes. — Wherever ma- 
laria is, there are mosquitoes; but we do not always find malaria 
where we find mosquitoes, as the species of mosquitoes necessary 
may not be present. 

From the above, it will be seen how strong is the presumptive 
evidence in favor of the inoculation theory of the disease, but we 
do not have to depend upon it to satisfy ourselves, for we have 
absolute experimental evidence which proves beyond all doubt 
that malarial [fever is a disease inoculated into man by the mos- 
quito. 

To the brilliant work of Manson, Ross, Bignami, Bastianelli, 
Marchiafava, and Grassi the world is indebted for the elucidation 
of one of the most important etiological questions in medicine 
to-day. 

I have already considered the development of the estivo- 
autumnal parasite within the mosquito, in a preceding chapter; 



66 ESTIVO- AUTUMNAL MALARIA 

in view of the etiological importance of the inoculation theory, I 
shall quote in detail a portion of the experimental evidence show- 
ing that estivo- autumnal (remittent) malarial fever is inoculated 
by the mosquito. 

Bignami was the first to succeed in producing estivo -autumnal 
fever through mosquito bites. His patient, one Sola, who had 
been an inmate in the Santo Spirito hospital for six years suffer- 
ing from a nervous disorder, but who had never had malaria, 
offered himself voluntarily as a subject for experiment. The fol- 
lowing is Bignami's record of the experiment. The mosquitoes 
used were from Maccarese, a very malarious district: 

"Sola slept in the room in which the infected mosquitoes had 
been liberated from September 26 to the end of October, 1898. 
During the latter part of October the patient complained of ma- 
laise and headache. On the afternoon of October 31 he had a 
slight elevation of temperature to 37.2° C. [99° P.]. On Novem- 
ber 1, at about 3 p. m., he was taken with a severe chill which 
lasted until five o'clock, the temperature rising rapidly to above 
39° C. [102.2° P.]. Between nine and ten o'clock a feeling of 
cold was again experienced. The fever continued all night, fall- 
ing in the early morning [November 2] to 38.2° C. [100.8° F.] 
and rising again that evening to 39.3° C. [102.7° P.]. The pa- 
tient was restless and complained of very severe headache, but 
there were no grave symptoms. In the night, about eleven 
o'clock, he had another chill of short duration. During this 
night the temperature remained above 39° C. [102.2° P.], and on 
the morning of November 3 rose above 40.4° C. [104.7° P.], the 
patient being very restless and complaining of much suffering. 
The fever broke in the afternoon with a gentle perspiration. 

"At quarter after five in the afternoon a hypodermic injection 
of one gram of quinine was given and again in the night. The 
fever fell, and at eight a. m. on November 4 the temperature was 
36.7° C. [98° F.]. The administration of quinine was continued 
during the following days, the patient continuing to have slight 
elevations of temperature which did not reach 38° C. [100.4° P.] 
except once, on November 6. From November 7 onward the pa- 
tient was entirely without fever, and rapidly regained his appetite 
and strength. 

"An examination of the blood made with the greatest care on 
November 2 gave negative results, no malarial parasites being 
found. On the morning of November 3 a few young annular 



EXPERIMENTAL ESTIVO-AVTUMNAL MALARIA 67 

parasites, motile and discoid, without pigment, and presenting the 
characteristic appearance of the parasites of estival fever, were 
found. These forms increased in number during the day, and 
were quite numerous during the afternoon hours. In some there 
was a beginning pigmentation at the border consisting of very 
fine granules of pigment. 

"We see, therefore, that there was produced experimentally in 
Sola a grave malarial fever with a temperature curve such as is 
frequently seen in a primary estivo- autumnal infection. The 
fever began briskly, continued with slight remissions from 
November 1 to 3, and began to fall on the evening of the latter 
day when the specific remedy was administered. The parasites 
found in the blood belonged to the estivo -autumnal species. 

" This is perhaps the first time that, in the primary estival 
infection acquired in the natural way, examinations of the 
blood have been made from the beginning of the fever. We find 
that after forty hours the parasites begin to be found, at first in 
small numbers, but rapidly becoming more and more numerous. 

"According to the opinion of all who followed this experi- 
ment, it was conducted in such a way as to silence all objections. 
Sola is a robust individual, notwithstanding his nervous malady, 
who has never in his life had malarial fever, and who has not 
been outside of the Santo Spirito Hospital for six years. The 
room where the experiment was conducted was an annex of the 
San Carlo ward, in which, within the memory of the hospital 
physicians, there has never been an autochthonous case of ma- 
larial fever, nor has there ever been any malaria in the neigh- 
boring houses. 

"Now in a room in the San Carlo ward of the Santo Spirito 
Hospital (Rome) Sola acquired a malarial infection produced by 
estivo -autumnal parasites, with a well-marked fever and symp- 
toms so grave as to call for the prompt administration of qui- 
nine. The fever indeed was exactly such a one as is ordinarily 
caught by laborers in the Roman Campagna in the summer and 
autumn months, a fever beginning with the typical curve of the 
estivo -tertian or sometimes with a continued curve. This iden- 
tical fever, such as prevails at Maccarese, was taken by Sola in 
a place when there was of Maccarese neither the water nor the 
air nor the soil, but the mosquitoes alone. We are then forced 
to the conclusion that the fever was acquired by inoculation by 
the mosquitoes." 



68 ESTIVO- AUTUMNAL MALARIA 

While in this case there could be no doubt that the mos- 
quitoes were responsible for the fever, it was not definitely set- 
tled just what species of mosquito was concerned, as there were 
three different species liberated in the room. After this experi- 
ment Grassi, Bastianelli, and Bignami worked with the Anopheles 
Claviger, and never failed to produce the disease when they were 
used. The following, a successful experiment performed by Bas- 
tianelli and Bignami, and quoted in their own words, is of great 
interest in many ways : 

"A patient suffering from a relapsing estivo- autumnal infec- 
tion, in whose blood were many crescents and round and flagel- 
lated bodies, slept, from December 10 to 18, in a room in which 
had been set free about fifty individuals of A. Claviger, brought 
from Maccarese. The temperature of the room was maintained 
at from 18° to 22° C. [64.4° to 71.6° F.]. Most of the mos- 
quitoes stung the patient, and became infected with crescent 
bodies, and subsequent examination showed in the middle intes- 
tine the characteristic forms in process of development. But it 
was also observed that the mosquitoes remaining in the room at 
the given temperature during the last days of December did not 
have in the intestines mature sporozoa with sporozoites, but only 
the growing forms. Evidently at a temperature of from 18° to 
22° C, the life -cycle of the parasite is completed very slowly. 
But these same mosquitoes, confined for a few days in an incu- 
bator at a temperature of 30° C. [86° F.], were found to con- 
tain forms of a later development. There were noted, enclosed 
in the intestines, typical capsules filled with sporozoites, and also 
broken and empty capsules, and in the salivary glands were 
numerous sporozoites. 

"When this fact was noted, three mosquitoes of this group 
were kept in an incubator at 30° C. for two days, and on January 

2 they were made to sting a new subject, A. R , who lent 

himself knowingly and willingly to the experiment. It is need- 
less to say that this man had never had malarial fever. On 
January 5 two of the same mosquitoes were made to sting the 
same person again, who then had been stung in all five times 
by three specimens of A. Claviger. 

"After this part of the experiment, the three mosquitoes were 
dissected and examined under the microscope, with the following 
results: 'i. Claviger, No. 1. In the intestines were found very 
many capsules with sporozoites, and some capsules which had 



EXPERIMENTAL EVIDENCE 69 

been ruptured and completely emptied of their contents. In the 
salivary glands were found two infected tubules ; in one were 
seen the cells swollen, of ovoid form, and filled with granules of 
uniform size. When pressure was made on the preparation there 
issued a very large number of sporozoites of typical form, uniform 
in appearance, and all of equal length; in the other tubule were 
also seen cells containing filiform sporozoites of characteristic 
appearance. 7 

"•'A. Glaviger, No. 2. — In the intestine were very numerous 
capsules, some still whole and filled with sporozoites, others rup- 
tured and shrunken, and containing a granular residuum of a pale 
yellow color. In some of these, ruptured capsules were seen, also 
brown bodies of various size and shape, some elongated, others 
short and deformed. In the salivary glands all the tubules were 
infected except one or two. In them were seen cells containing 
typical sporozoites, cells filled with granules similar to those de- 
scribed in the case of A. Glaviger, No. 1, and cells filled with 
round hyalin bodies of variable size. In addition there were also 
found typical filiform sporozoites along the excretory ducts of the 
gland.' 

" *A. Glaviger, No. 3.— The intestine was filled with mature 
sporozoa. Many capsules were broken and shrunken, and con- 
tained a pale yellow detritus; others contained a large central 
body of granular aspect, surrounded by a hyalin halo and without 
any recognizable structure. These were possibly mature sporozoa 
in process of degeneration. The salivary glands were not found 
infected. From the results of these examinations we may con- 
clude that of the three specimens of A. Glaviger employed, only 
two had inoculated the patient with malaria.' 

"On the evening of January 10 the patient had a sense of 
heat and a headache, but the temperature was normal. On Jan- 
uary 11, 12, and 13, there was no fever and the patient felt well. 
On January 14, that is, after from nine to twelve days' incuba- 
tion, there was no fever until eight o'clock in the morning, but 
then the temperature began to rise rapidly and reached 39.5° C. 
[103.1° F.] at noon. From this time the fever remained con- 
tinuous up to January 18. The temperature fell to normal at six 
in the morning of the 18th. [Two grams of quinine were given 
hypodermically on the 16th, and repeated on the 17th, and re- 
covery was complete and rapid.] 

"On examination of the blood on the morning of January 16 



70 ESTIVO- AUTUMNAL MALARIA 

there were found scanty estivo- autumnal parasites with very fine 
pigment -granules at the periphery. There were found, also, Plas- 
modia without pigment and with granules, in normal red blood- 
corpuscles and in brassy bodies. The parasites disappeared after 
the exhibition of quinine on January 17. Thus the infection was 
rapidly cut short and no crescent bodies were seen. 

"We have in this case a typical example of estivo -autumnal 
infection, beginning with a continued fever, as is usual with this 
group of malarial infections. The course of the disease was in 
every respect identical with that in the first case of malarial fever 
experimentally induced by the stings of mosquitoes [the Sola case 
described by Bignami]." 

From the above it will be seen that the disease was caused by 
the bites of only two insects, and, as pointed out by Marchiafava, 
this is not surprising when one considers the vast number of 
sporozoites in the infected salivary glands of a single mosquito. 
There is no reason to doubt that one mosquito might infect 
a number of individuals. From the experimental evidence which 
has accumulated, of which I have only given a small portion, we 
must conclude that estivo -autumnal malarial fever, and in fact, 
all malarial fevers, are produced in man by inoculation through 
the bite of certain species of mosquitoes, and while it cannot yet 
be proven that this is the only manner of infection, it is but rea- 
sonable to suppose that such is the case. 

The most striking recent confirmation of the mosquito theory 
is found in the experiments of Sanbon and Lowe. These investi- 
gators spent an entire summer in the most malarious portion of 
the Roman Campagna, residing in a mosquito proof hut. During 
the day the time was spent mostly out of doors, but at evening 
and during the night the time was spent indoors. Neither investi- 
gator developed malaria, although many individuals residing in 
the same locality, without protection from mosquitoes, suffered 
severely from the disease. 



CHAPTER IX 

TRANSMISSION BY INOCULATION FROM MAN TO MAN— INCUBA- 
TION— IMMUNITY— SPONTANEO US BECO VERY 

Transmission by Inoculation fkom Man to Man. — I have, 
in a previous chapter (Chapter V), considered this method of the 
transmission of estivo- autumnal fever, and from the experimental 
data there given two facts are demonstrated, viz. : 

First, that the malarial fevers may be transmitted to a healthy 
individual by the inoculation of blood from an individual suffering 
from the disease. 

Second, that the type of fever inoculated is always reproduced 
in the individual — that is, if a healthy individual is inoculated 
with blood containing the tertian malarial parasites, tertian fever 
will follow; if with blood containing the estivo -autumnal para- 
sites, estivo -autumnal fever will follow, etc. 

Such inoculation experiments also prove that the mosquito is 
not absolutely necessary to the transmission of the disease experi- 
mentally; but it is doubtless a fact that it is essential in nature, 
and it certainly is in the extra-corporeal cycle of existence of the 
malarial parasites. 

Incubation. — Much has been written as to the period of incu- 
bation of the malarial fevers, but I will only consider here that 
phase of our subject which relates to the incubation of the estivo - 
autumnal fevers. 

The period of incubation is the time elapsing from the infec- 
tion of the individual with the parasite to the first clinical symp- 
toms of the disease. Obviously this is often a very difficult point 
to determine, and it is only occasionally that one can be sure of 
his data upon the subject. Hertz believes that the incubation 
varies from six to twenty days, and I am sure, from personal 
observation, that the incubation period can be even longer than 
twenty days. Some authorities have claimed, upon entirely in- 
sufficient data, that only a few hours may elapse from infection 
to the outbreak of the disease; but all experience is absolutely 
negative of such an opinion. As far as I know, the most satis- 

(71) 



72 ESTIVO- AUTUMNAL MALARIA 

factory datum which we possess upon the question of the incubation 
of the estivo- autumnal fevers is that given by Marchiafava and Big- 
nami, who were so fortunate as to observe three cases in which 
they were certain of the time of infection. These cases are here 
given in these authors' own words: 

" Case I. — A robust young man, twenty-five years of age, 
living in the central part of Rome, had never had malarial fever. 
On November 4, 1894, he was obliged to go to Sermonetta, a 
notoriously malarious town near the Pontine marshes. He arrived 
in the city at ten o'clock, slept that night, tormented with swarms 
of mosquitoes, in a house on the outskirts of Sermonetta, and in 
the morning returned to Rome, where he resumed his usual occu- 
pation. For sis days he was in good health; then he had two days 
of malaise and on November 13, that is to say nine days after his 
stay in Sermonetta, he was taken down with an estivo-autumnai 
tertian fever, the parasites of this form being found in the blood. 

"Case II. — An engineer, living in Rome, who had never suf- 
fered from malaria, was constrained by the duties of his calling 
to pass a day, in October, 1895, in a place in the Pontine marshes, 
and he slept that night in a. cabin in poor repair in which were 
many mosquitoes. At the end of ten days an estivo-autumnai 
infection, with irregular fever, developed, of which he had several 
relapses, extending up to the following spring." 

" Case III. — A lady who for many years had enjoyed good 
health passed a week at Fiumicino in the month of October, 1894. 
Three days after her return to Rome an estivo-autumnai malarial 
fever declared itself, and, not being promptly treated, developed 
into a choleraic pernicious attack; following this the patient re- 
mained profoundly anemic, with a sanguinolent diarrhea, and 
died at the end of a few weeks." 

From the above cases it will be seen that the period of incuba- 
tion was from nine to ten days. 

Much data have been collected regarding the incubation period 
from the inoculation experiments, and I have given the most 
important. 

Bastianelli and Bignami found in estivo-autumnai fever the 
maximum period of incubation was five days, the minimum two, 
mean three days; Bignami, maximum ten, minimum six. 

Mannaberg, seven cases, three to fourteen days, mean six and 
a half; Marchiafava and Bignami, maximum fourteen days, mini- 
mum two, mean six and one-tenth days. 



PERIOD OF INCUBATION 73 

All these observers have found that the greater the amount 
of infected blood inoculated, the shorter was the period of 
incubation. 

The chief fault with the above data is that it was obtained by 
the inoculation of the disease in an unnatural manner. We know 
to-day that malaria is due to the inoculation of sporozoites from 
the mosquito into man. In the inoculation of blood containing 
only the forms of the parasite belonging to the human cycle it is 
reasonable to suppose that the period of inoculation will be shorter 
than is the case when the mosquito transmits the sporozoites to 
man, and that it is so has been proved experimentally, for 
Marchiafava and Bignami have found that an individual stung by 
mosquitoes which had sucked blood containing crescents devel- 
oped estivo- autumnal fever in from nine to twelve days, almost 
the exact period observed in the cases quoted, where infection 
occurred in malarious localities. But though the period of incu- 
bation of these fevers is doubtless, for the great majority of cases, 
from nine to twelve days, cases do occur which show a much 
longer period of incubation, sometimes of weeks or months. 
Sternberg quotes the cases of certain sailors who were infected 
while their ship lay two days in port, and who developed the 
disease, one after forty -eight, the other after one hundred and 
eighty -four days after leaving the port. I am fully convinced 
that estivo -autumnal fever may have a very long period of incu- 
bation, and in support of this fact may mention the following 
personal experience: 

A surgeon of the United States Army, August, 1899, was in 
camp outside of Havana, Cuba, in a malarious district. In Sep- 
tember he returned to New York, and then was ordered to San 
Francisco. From August, 1899, until March, 1900, he enjoyed 
good health, but during March he suffered from general malaise 
and a chronic diarrhea. On April 1 he had a slight chill and his 
temperature rose to 106.2° F. His blood showed numerous ring- 
forms and pigmented forms of the estivo -autumnal parasites, and 
though this attack was quickly overcome by quinine, he has had 
several relapses since. 

In this case I am convinced that his infection occurred while 
in camp at Havana, for the reason that estivo -autumnal fever is 
not present in New York city or San Francisco, and he was in 
no other places than these after coming from Havana. In this 
ease, then, the incubation period was at least seven months. 



74 ESTIVO- AUTUMNAL MALARIA 

As to the explanation of such long periods of incubation, I 
believe the theory advocated by Thayer to be the true one, i. e., 
that the parasites multiply and perform their life -cycle, but in 
such small numbers that they give rise to no observable clinical 
signs. I am the more convinced of this, as it is borne out in the 
examinations of blood in cases of soldiers returning from the 
tropics. In the United States General Hospital at San Francisco 
the blood of every case admitted is examined for the malarial 
parasites, whether or not clinical symptoms are present. This 
routine practice has led to the surprising discovery that at least 
40 per cent of the cases whose blood contains the malarial para- 
site have no clinical symptoms of the disease, and a large pro- 
portion of these cases show the estivo- autumnal parasite to be 
present. Many of these cases have shown the parasites for weeks, 
and the life -cycle in the ordinary tertian cases followed, in small 
numbers, with no clinical symptoms present; and I consider that 
this proves beyond all doubt the truth of Thayer's theory and 
shows conclusively the reason for long periods of incubation. It 
is not too much to say, that if this routine method of examining 
the blood of every patient in malarious districts, or coming from 
such districts, could be followed in every hospital, our ideas re- 
garding the relation of malaria to other diseases would be greatly 
modified. I shall discuss more thoroughly this subject in the 
chapter devoted to the diagnosis of estivo-autumnal fevers. 

The question arises, How long will the susceptible individual 
live in a malarious country before acquiring the disease? It is 
impossible to answer this question for all cases; but in the great 
majority of instances an individual residing in a region infected 
by estivo-autumnal fever will acquire the disease in from three 
weeks to two months, provided he is exposed. Of the hundreds 
of cases of malaria occurring in our soldiers in Cuba, almost 95 
per cent gave a history of being there for from two to six weeks 
before the onset of the disease. One month was the most common 
period given by the men as intervening between landing in Cuba 
and the first chill. 

As in many other diseases, the length of the period of incu- 
bation varies with the amount of the infecting agent, the physi- 
cal condition of the infected individual and his surroundings, 
as regards exposure, hardship, heat and cold, insufficient nour- 
ishment, etc. 

Immunity. — Immunity to estivo-autumnal fever undoubtedly 



IMMUNITY 75 

exists, and such immunity may be considered under the following 
divisions: Racial immunity, congenital immunity, and acquired 
immunity. 

Racial Immunity. — It has been said that certain races of 
mankind are immune to the malarial fevers. This statement is 
undoubtedly false and cannot be proved by facts. While this 
is so, it is a well -recognized fact that some races are more resist- 
ant to malaria than others. The black races are relatively 
immune to the disease, but the immunity is undoubtedly acquired. 
Plehn has demonstrated that the Kamerun negroes rarely have 
malarial fever, and generally recover spontaneously; whereas 
Europeans suffer very severely in the same locality. The same 
is said of the Malays by Martin, while Tommasi-Crudelli has 
noticed differences in the resisting power of the inhabitants of 
certain localities of Italy. 

While such differences in the susceptibility to malaria undoubt- 
edly exist, they may all be explained by the theories of acquired 
immunity, and it is true that no people inhabiting the world are, 
as a race, immune to the malarial diseases. 

Congenital Immunity. — There undoubtedly exist many people, 
living in the most malarious localities, who have never suffered 
from the disease, and to them we must accord the fullest degree 
of immunity. This immunity is in all probability congenital, 
and has even been proved, in a few instances, to be a family 
characteristic. 

Acquired Immunity. — Long residence in a malarious country 
will, undoubtedly, if the individual survives, confer upon him a 
relative immunity to the disease. As is the ease with other dis- 
eases, repeated attacks of malaria in man will, in time, render 
him less liable to further attacks. In other words, the malarial 
poison produces certain changes in the human organism which 
render it at least partially immune to future attacks. This im- 
munity, however, is often gained at the expense of the vitality 
of the individual, and the penalty inflicted is a chronic malarial 
cachexia, which markedly lowers the health of such so-called 
immunes. The history of acquired immunity is simply that of 
repeated attacks of the malarial fever, each one a little less severe 
than the preceding, until at last a spontaneous cure is effected. 

The immunity thus acquired may be lasting, but, as a rule, 
unusual hardship, privation, ill health or removal to a new locality 
will destroy it, and he who thought himself immune learns by 



76 ESTI VO-A VTUMNAL MALARIA 

sad experience that absolute immunity to the malarial fevers is 
so rare as to be almost non-existent. 

Spontaneous Recovery. — It would seem well in connection 
with immunity to review the question of spontaneous recovery 
from the estivo- autumnal fevers. By spontaneous recovery we 
mean the dying out of the infection without the intervention of 
medicines. In the pre -quinine days this was the way in which 
most malarial affections were cured, and, as often happens, the 
physician received the credit due to nature. To what, then, 
when spontaneous recovery occurs, is it due ? No one knows 
exactly, but some deductions can be drawn from the exami- 
nations of the blood in such cases, and the known facts regard- 
ing this termination in the disease. 

In the first place, examination of the blood in cases which 
are undergoing spontaneous recovery shows a gradual diminution 
in the number of parasites present. Together with this dimi- 
nution, which is progressive, certain degenerative changes are 
noted, such as vacuolation, fragmentation, etc., of the matured 
organisms. Numerous pigmented leucocytes and much free pig- 
ment are also often found* Many times, in cases recovering 
spontaneously, the entire life -cycle of the parasite may be fol- 
lowed in the blood, in tertian or quartan fever, but they are so 
few in number that no clinical symptoms are produced. I have 
repeatedly observed this fact. 

Metchnikoff and his adherents have laid much stress upon the 
relation of phagocytosis to spontaneous recovery, but there are no 
experimental data or observations sufficiently convincing to prove 
the phagocytic theory. I have already considered the subject 
of phagocytosis as it is related to estivo-autumnal fever, and 
although it is doubtless a factor in the process of spontaneous 
recovery, it is certainly only a secondary one. It must, I think, 
be admitted that the phagocytic cells, by destroying a certain 
number of parasites and removing from the blood large quan- 
tities of pigment and excrementitious matter, help in producing 
recovery from the infection, but phagocytosis, per se, is not the 
cause of spontaneous recovery. 

The question arises: To what is due the degenerative changes 
noted in the parasites in cases undergoing spontaneous recovery? 
Mannaberg believes that the fever present is detrimental to the 
growth of the parasites; but this can hardly be so, for often 
cases showing the highest temperature present large numbers of 



SPONTANEOUS RECOVERY 11 

parasites in the blood, all of them in normal condition. Mar- 
chiafava leans to the theory that in malaria, as in bacterial 
diseases, the parasite gradually loses its virulence. In opposi- 
tion to this it may be urged that the cause of malaria is not a 
bacterium, but a parasite belonging to the animal kingdom, 
totally different in its structure and life-history, and that there 
is absolutely no evidence of such diminution of virulence. 
Personally, I do not believe that the argument of diminished 
virulence can be applied in this case, as even in bacteria such 
diminution does not lead to disintegration. If, then, neither the 
fever nor the theory of diminished virulence hold good, as 
explanations of the death of the parasites, to what is their 
degeneration due? In answer, I would say: to certain antitoxic 
substances elaborated by the white cells and excreted, and to 
others liberated by the breaking down and disintegration of the 
leucocytes. 

It is an established fact that some of the white cells, espe- 
cially the eosinophiles, excrete certain substances which are very 
destructive of parasitic life, and what is more natural to suppose 
than that these antitoxic materials, as they may be called, are 
prejudicial to the development of the parasites of malaria. This 
excretory function of the leucocytes is, in my opinion, far more 
important in the production of spontaneous recovery than is 
phagocytosis. As a matter of fact, phagocytes are often more 
numerous in pernicious cases, resulting fatally, than in mild 
cases, whereas the coarsely granular oxyphile or eosinophile is 
always more numerous in mild cases than in severe ones, and 
is very often very largely in excess in the cases undergoing 
spontaneous recovery. As a rule, in estivo- autumnal fever, 
the appearance of crescents in the blood is coexistent with the 
spontaneous disappearance of the clinical symptoms and the 
intracellular parasites. It would seem from this that the life- 
cycle of the parasite within the human body had ceased, the 
extra -corporeal form of the parasite having been produced. 
Certain it is that the appearance of crescents and the disappear- 
ance of other forms of the parasites denote spontaneous recovery 
from the disease. 

To sum up, then, the causes of spontaneous recovery, I would 
place them in the following order, as regards their importance: 

1. Production and excretion of certain substances, bactericidal 
and antitoxic in nature, by the coarsely granular oxyphile or 



78 ESTIVO- AUTUMNAL MALARIA 

eosinophile, which substances cause the death and degeneration 
of the parasites of malaria. 

2. Disintegration of the leucocytes and liberation of certain 
antitoxic and bactericidal substances, having a similar action. 

3. Phagocytosis, i. e., the engulfing and digestion of the 
parasites. All these processes, without doubt, occur simultane- 
ously, and to them is due, I believe, the spontaneous cure of the 
disease. 

Often, however, spontaneous recovery is more apparent than 
real. The fever may disappear, together with many or most of 
the clinical symptoms, only to be followed in a week or ten days 
by a relapse. Often, also, after spontaneous recovery seems to 
have occurred, an examination of the blood will demonstrate the 
presence of a few estivo- autumnal parasites, and these may persist 
for days and even weeks without causing any noticeable symp- 
toms. Again, the parasites may entirely disappear from the per- 
ipheral blood, but blood obtained by puncture of the spleen will 
show numerous parasites in all stages of development. 

Indeed, a sharp distinction should be drawn between apparent 
and real recovery in the estivo -autumnal malarial fever, and per- 
sonally, after a large experience with these fevers, I am convinced 
that it is impossible to say when a patient is actually cured, for 
relapses occur so frequently that a guarded statement concerning 
cure is always advisable. 



CHAPTER X 

GENERAL PATHOLOGY OF THE ESTIYO - AUTUMNAL FEVERS— 
CHANGES IN THE RED CORPUSCLES— MELANEMIA — ANEMIA — 
THE URINE — THE ETIOLOGY OF THE FEVER. 

Pathology of the Blood. — The pathological changes which 
occur in the blood as the result of estivo- autumnal infection are 
due to primary and secondary causes. The primary cause is the 
infection of the red cells with the parasites and the changes 
brought about by such infection; the secondary is the anemic 
condition, which is the inevitable result of malarial infection. 

The Primary Changes in the Blood.— These changes are 
brought about by the invasion of the red cells by the estivo- 
autumnal parasites. The chief are: 

Changes in Form. — Red corpuscles invaded by the estivo- 
autumnal parasites are generally smaller than normal, and often 
appear shrunken and wrinkled or crenated. This is especially 
true of those infected with the quotidian estivo -autumnal parasite. 

Changes in Color. — Such infected corpuscles are often a very 
dark olive -green in color and present a brassy appearance. This 
change is also most marked when the corpuscles are infected 
with the quotidian parasites. These ' ; brassy bodies" are most 
numerous after a paroxysm, when the parasites have reached 
the pigmented stage, and are also more numerous after the 
administration of quinine. This change is thought to be, by 
most authorities, due to a necrosis of the infected red cell. 

Retraction of Hemoglobin in Infected Corpuscles. — Many in- 
fected red corpuscles show a retraction of the coloring matter 
at some portion of their periphery, small areas being entirely 
colorless. Often the hemoglobin membrane, as it may be called, 
is retracted about the contained parasite, and this is notably so 
in the case of crescents, which often appear as though enclosed 
within a thin greenish web. It is to this change in the red cell 
that the "bib" and double outline of the crescent is due. 

Phagocytes. — The occurrence of pigmented leucocytes and 
phagocytes has already been discussed. 

(79) 



80 ESTIYO- AUTUMNAL MALABIA 

Melanemia. — The occurrence within the blood, either free or 
within leucocytes, of malarial pigment, is known as melanemia. 
This pigment may be brown, brownish yellow or black in color, 
and may occur as blocks, granules, rods, grains, irregular clumps, 
fine needles, or cylindrical, polyhedral, circular or irregular 
masses. This condition is only present in malaria, and is often 
of great service in diagnosis where the parasites are few in 
number or in chronic malarial poisoning. 

Historical. — It would be unprofitable here to enter fully into 
the history of the many observations which have been made upon 
this subject, but a short resume will be given of the most im- 
portant. 

Meckel,* in 1847, was the first to describe pigment occurring 
in the blood, and his observations were confirmed by Virchowt 
and Frerichs. All of these investigators considered that the pig- 
ment was from the spleen or liver, Frerichs believing it to be 
from the spleen only. 

Meigs and Colin wrote very excellent descriptions of the con- 
dition, but to Arnstein J we owe the discovery that the pigment 
arises in the circulating blood. Arnstein's theory is as follows: 
During the fever the red cells are destroyed and the pigment 
formed is liberated and taken up by the leucocytes and deposited 
in the tissues. 

Kelsch§ studied the subject very thoroughly, and came to the 
conclusion that the destruction of the red cells gave rise to the 
pigment which remained in solution in the blood until it became 
saturated, when it was precipitated in granules which were then 
engulfed by leucocytes. 

Laveran, Marchiafava, and CelliH demonstrated that the 
pigment is not formed after the disintegration of the red cells, 
but is formed during the growth of the malarial parasites, 
within them; being, in fact, the changed hemoglobin of the 
corpuscles, which has been absorbed by the parasites during 
their growth. 

Two varieties of pigment are present in estivo- autumnal fever: 
one, melanin, or black pigment, present both in the blood and 
tissue; the other, hemosiderin, or yellow pigment, present only in 
the tissues. The first gives no reaction for iron; the second does. 

*"Zeitsehr. f. Psych.," 1847, p. 198. § "Arch de Physiologic," Second Series. 

tVirch, Arehiv, 1849, 11, 587. II " Commentaria clin. de Pisa," 1879. 

X Virch, Arehiv, 1874, Bd. lxi, 494.! 



ORIGIN OF MALARIAL PIGMENT 81 

As regards the origin of the two varieties, I am fully in accord 
with Bignami, who says: "The melanemia, index of an acute in- 
fection, is derived only from the direct transformation of hemo- 
globin into melanin through the action of the parasites within the 
red corpuscles, as Marchiafava and Celli have demonstrated; that 
the melanosis of the viscera, spleen, liver, bone-marrow, etc., 
index of a previous infection, has a double origin. In chief part 
it is derived from the melanemia, that is, from the deposition in 
the viscera of the black pigment formed during the acute infection 
in the circulating blood; in part it has a local origin, that is, it 
is derived from the slow transformation of the blocks of ochre- 
colored pigment which are deposited or formed in the spleen and 
in the other viscera from the enormous quantity of altered red 
blood-corpuscles, which, in grave infections, die before the direct 
action of the parasites has transformed their hemoglobin into 
black pigment." 

Chemical Characteristics of Melanin. (The Black Pigment.) — 
The pigment is decolorized by the potassium and ammonium 
salts; is soluble in sulphide of ammonium and insoluble in the 
strong acids. 

No trace of iron has ever been demonstrated in it, but this 
does not, by any means, prove that it is not present. In all 
probability, melanin is closely allied to hematin, as is held by 
C arbour. 

Distribution of Melanin. — The melanin formed from the hem- 
oglobin of the red cells during the growth of the parasite is, 
after its segmentation and the destruction of the red cells, 
liberated in the blood-plasma, when it is taken up by the leuco- 
cytes and deposited in certain tissues, especially the brain, liver, 
and spleen. 

The Yellow Pigment. — There occurs within the tissues (never 
in the blood) in cases of estivo- autumnal fever, a large amount 
of a golden yellow pigment, which is scattered throughout the 
tissues of the liver, spleen, and bone-marrow. It occurs as very 
fine grains, larger masses of an amber color, and as large blocks 
of a golden yellow color. This pigment arises from the hemo- 
globin of the red cells also, and has been called by Neuman* 
hemosiderin. This pigment is especially abundant in fatal cases 
of pernicious estivo- autumnal fever and occurs chiefly in the 
liver and spleen. 

* Vireh, Arehiv, Bd. esxi, p. 318. 



82 ESTIVO -AUTUMNAL MALARIA 

Chemical Characteristics of Hemosiderin. (The Yellow Pig- 
ment.) — It is insoluble in strong acids, caustic potash, water, 
and alcohol; turns black when treated with sulphide of am- 
monium, and gives a blue color when treated with ferrocyanid 
of potassium, which is characteristic of hemosiderin. It will be 
seen that this pigment, unlike melanin, gives an iron reaction. 

Distribution of the Yellow Pigment. (Hemosiderin.) — This 
pigment is present only in the tissues, and is most abundant in 
the liver and spleen. In the liver it is present mostly in the 
hepatic cells, unlike melanin, which is never found within these 
cells. In the spleen it is found within the cells or lying free in 
the splenic sinuses. 

The Anemia of Estivo- autumnal Fevers. — In all forms 
of estivo -autumnal fever there is a reduction in both the red 
and white blood -corpuscles. This reduction is more marked than 
in the ordinary intermittent fevers, and is due to the action of 
the parasites upon the corpuscles containing them; the action of 
poisonous material elaborated and set free by the parasites, and 
to inhibited function of the blood -producing glands, due to the 
changes brought about in them by the malarial disease. 

The greatest factor in the destruction of the blood -cells is 
undoubtedly the direct action of the estivo -autumnal parasites. 

The Bed Corpuscles. — Kelsch* has investigated the subject very 
thoroughly, and has found that a reduction in the number of 
red cells follows every paroxysm; but it has also been found 
that during the paroxysm they may be increased. This reduc- 
tion may be very great, Kelsch having observed only 500,000 to 
the cubic millimeter. In ordinary cases, after the fever has 
continued two or three days, the red cells will often fall to 
2,000,000 or less per cubic millimeter. A peculiar fact about 
the anemia is, that while during the first few days the reduction 
of red cells is marked, the continuance of the disease, after a 
certain amount of anemia has been produced, is not character- 
ized by a further reduction, there being no progressive falls. 
This is true in the majority of cases, but not in all. 

In the pernicious forms of estivo -autumnal fever the reduc- 
tion in red blood-cells is very rapid, a fall to 1,000,000 per 
cubic millimeter being often observed in twenty-four hours. If, 
however, the patient has suffered before from malaria, and is 
already anemic, the reduction is less, averaging a loss of about 

*Archiv. de Physiologie, 1875, 690. " " 



THE BED BLOOD COBPUSCLES 83 

1,000,000 in the twenty-four hours. It must not be supposed, 
however, that all cases of pernicious malaria show so great a 
reduction in the red corpuscles. 

The return to the normal number of the red corpuscles is 
generally rapid after a mild or even severe infection which has 
been promptly stopped by treatment; but cases untreated, or in 
which many relapses have occurred, are followed by a chronic 
and persistent anemia, which is one of the most marked charac- 
teristics of people inhabiting malarial regions. Dionisi* has 
contributed some very valuable data concerning the anemia of 
the estivo- autumnal fevers, and his conclusions are here given: 

(In one case under my own observation the red cells fell 
to 690,000 per cubic millimeter, in three days, but increased 
to 2,100,000 per cubic millimeter in about three weeks, after 
treatment.) 

"1. In estivo -autumnal fever, the reduction in the number 
of red blood -corpuscles bears a direct relation to the number of 
organisms. Where the parasites are numerous there is a con- 
stant reduction of from 200,000 to 1,000,000 with each febrile 
paroxysm; where the parasites are scanty the reduction is less. 

"2. When crescentie bodies are present in addition to the 
other forms, they seem to exert no influence on the blood- 
changes. 

"3. When, after a paroxysm, the number of corpuscles has 
suffered a sudden and very marked diminution, the succeeding 
paroxysms may be followed by but a slight reduction only, or 
even by an increase. 

"4. In relapses, the reduction per paroxysm is less than in a 
primary infection. 

"5. In infections determined by the amoeboid forms (acute 
estivo -autumnal infection) there is, during apyrexia, no complete 
return of the red corpuscles to their normal number. Some 
attempts at restitution may be seen during the first several days 
of apyrexia, while after this, during perhaps eight to fifteen 
days, there may be a steady reduction of from 100,000 to 500,000 
red blood -corpuscles without the appearance of any parasites in 
the blood. 

"6. Only after" marked and continuous reductions following 
each paroxysm does there occur in the afebrile period a relative 
restitution of the red blood -corpuscles; this may be slow or rapid. 

*Lavori del III Congress de Soeieta di Medicina Interna, Milan, Oct,, 1890, page 169. 



84 ESTIVO- AUTUMNAL MALARIA 

"7. If the increase in the corpuscles has begun, the presence 
of crescents has no deleterious effect. 

"8. In tertian and quartan fevers the same changes are 
observed, excepting that in the afebrile period there is a rapid 
and almost complete restitution of the red blood -corpuscles, 

"9. The colorless corpuscles follow the same course as the 
red, both in apyrexia and fever. In later periods, however, 
when the red corpuscles have increased, there may still be a 
marked diminution in the colorless element. 

"Bastianelli noted the association of the anemia of cachectics 
with actual changes in the marrow produced by the infection." 

The White Corpuscles. — It may be said in general that the 
reduction in the white corpuscles, or leucocytes, corresponds with 
that of the red. During the paroxysm there is an increased 
number of leucocytes in the peripheral blood, while between the 
paroxysms they are very markedly decreased. They are always 
diminished in number relatively to the red corpuscles, and this is 
especially true of the blood of patients suffering from chronic 
malarial poisoning. The reduction in the leucocytes is observed 
in all cases of simple tertian or quotidian estivo- autumnal fever; 
but the reverse is true of cases of pernicious estivo -autumnal 
fever, in which they are very often greatly increased. Kelsch 
has observed as high as 35,000 leucocytes per cubic millimeter in 
the pernicious infections. In one case of fatal comatose perni- 
cious estivo -autumnal fever which I observed, the leucocytes were 
very greatly increased, averaging at least one to every one hun- 
dred and twenty red corpuscles. This marked increase in the 
number of leucocytes in pernicious malaria is a strong argument 
against the theory, advocated by Metchnikoff and his adherents, 
that the leucocytes play the most important role in the sponta- 
neous cure of the malarial fevers. 

Reduction of Hemoglobin. — Besides the reduction in the red 
and white corpuscles, there is generally a marked reduction in the 
hemoglobin, in the estivo -autumnal fevers. This subject has been 
thoroughly investigated by Rossoni,* whose conclusions are here 
given : 

"1. No acute infection results in as active a deglobulization 
as does malarial fever. 

"2. In all cases of malarial fever there is an immediate di- 
minution in the number of corpuscles and the amount of hemo- 

*"Lavori del congresso societa di medieina interna," Rome, Oct., 1889, p. 121. 



POST -MALARIAL ANEMIA 85 

globin. This loss generally bears a direct relation to the duration 
of the infection. In pernicious cases, however, a diminution of as 
much as two -thirds of the total amount may take place in from 
one to three days. 

"3. The gravity of pernicious cases does not always bear a 
direct relation to the extent of the loss in hemoglobin. 

"4. The destruction of hemoglobin and corpuscles bears, gen- 
erally, a direct relation to the number of parasites in the blood. 
Occasionally, however, cases with high fever and marked losses 
in hemoglobin and corpuscles may show but few parasites in the 
circulating blood. A long -continued diminution of hemoglobin is 
often associated with the presence of crescents. 

"5. The loss in hemoglobin and corpuscles is rarely evident 
during the paroxysm, but begins with apyrexia and may continue 
for several days afterwards. 

"6. Recovery from malarial anemia is slower than from the 
other acute anemiae. 

"7. Usually the hemoglobin and corpuscles are equally di- 
minished, but sometimes the hemoglobin is a valuable point in 
differential diagnosis between malarial fever and enteric fever or 
pneumonia. 

"8. The restitution of the hemoglobin in malarial anemia is 
often incomplete, and individuals living in malarial districts have 
often a slightly smaller percentage of hemoglobin than those living 
elsewhere." 

Post-Malarial Anemia. — In the majority of patients suffering 
from repeated attacks of malarial fever, of the estivo- autumnal 
variety, in whom a cachectic condition is present, there is present 
a greater or less degree of anemia, the red blood cells seldom 
numbering over 3,000,000 per cubic millimeter, and often not 
over 1,500,000 per cubic millimeter. In severe cases nucleated 
red cells are sometimes seen, and poikilocytosis is often present. 
In these cases the leucocytes and lymphocytes are relatively in- 
creased, while the polymorphonuclear leucocytes are decreased. 

From their researches Dionisi and Bignami* have separated 
four types of post -malarial anemia, as follows: 

"1. Anemias in which the examination of the blood shows 
alterations similar to those observed in secondary anemia, from 
which they differ only in that the leucocytes are diminished in 
number. The greater part of these cases go on to recovery; a 

*"Cent. fiir alleg., Path., u. Path., Anat.," 1894, v. No. 10, p. 422. 



86 ESTIVO- AUTUMNAL MALARIA 

few, without any further change in the hematological condition, 
pursue a fatal course. 

"2. Anemias in which the examination of the blood shows 
alterations similar to those seen in pernicious anemias — presence 
of gigantoblasts. These cases end fatally. 

"3. Anemias which are progressive, as the result of compen- 
sation by the marrow for losses brought about by the infection. 
At autopsy the marrow of the long bones is found to be wholly 
yellow, while the marrow of the flat bones is also poor in nucleated 
red corpuscles. 

"4. Chronic anemias of the cachectic, which differ from the 
above-mentioned tj r pes by clinical and anatomical characters, in 
that the special symptoms of malarial cachexia prevail, while one 
observed post-mortem, a sort of sclerosis of the bone -marrow. 
The marrow of the long bones is red and many are necrotic; the 
nucleated red blood- corpuscles are very rare, and the colorless 
polymorphonuclear corpuscles are present in small numbers." 

There is some difference of opinion as to whether or no the 
decrease of leucocytes, noted in acute paroxysms, is absolute or 
only apparent. Marchiafava and Bignami say regarding it: "In 
our opinion, therefore, leucopenia during an acute infection does 
not depend upon a real diminution in the number of leucocytes, 
but upon a change in their distribution caused by the tendency of 
the white cells to accumulate in the vascular areas in which the 
blocks of pigment, mature parasites, etc., in short, the substances 
which they take up, accumulate." 

However this may be, the fact remains that the estivo- 
autumnal fevers are never accompanied by a leucocytosis unless 
that leucocytosis be due to some complication, as pneumonia. 

The Urine in Estivo- autumnal Malarial Fever. — In all 
forms of estivo -autumnal malarial fever the urine shows a greater 
or less number of pathological conditions to be present. The 
urine in this class of cases has been very thoroughly studied by 
Rem-Pici,* and to him we owe most of our knowledge concerning 
the changes which occur. 

Amount. — As a rule, during the acute attacks of estivo- 
autumnal fever, the amount of urine is diminished. During the 
paroxysms the amount of urine passed is increased, but is 
diminished during the apyrexial stage. I observed recently an 
interesting case in which the patient recognized the impending 

* " Polielinico Roma," 1893, I, p. 131. 



TEE URINE 87 

occurrence of the paroxysms by the greatly increased amount of 
urine which he passed. In rare cases the greatest amount of 
urine is passed after, instead of during, the attack. 

Polyuria. — While in the tertian and quartan fevers conva- 
lescence is often marked by the occurrence of polyuria, this is 
not so true of the estivo-autumnal fevers. A slight polyuria is, 
however, very common, and is probably much more so than is 
generally known. Now and then a very marked polyuria will 
be observed, as in a case observed by me, following a tertian - 
autumnal attack, in which for weeks the patient passed from 
20,000 to 25,000 cubic centimeters of urine per day. 

This was the most marked case of polyuria following any 
malarial fever which I have ever seen. 

Color. — As in all febrile diseases, the color of the urine is 
increased, being usually reddish. It is often turbid, and deposits 
urates or phosphates upon standing. The color of the urine in 
the polyuria of convalescents is usually a pale lemon -yellow. 

Acidity. — As a rule, the acidity is increased when the urine 
is diminished in amount, and is about normal when it is secreted 
freely. 

Specific Gravity. — During the attack the specific gravity is 
increased; but, on the whole, there is little variation from 
normal in the specific gravity. The specific gravity of the urine 
in polyuria is low, being from 1.005 to 1.010. 

Total Solids. — The total solids are increased, especially during 
the paroxysm. 

Urea. — The amount of nitrogen excreted in the twenty -four 
hours is increased, the increase of the urea and nitrogen being 
most marked during the paroxysm. Sometimes this increase is 
noted before the fever, but, in the vast majority of cases, only 
directly afterwards. During the apyrexial periods the amount 
of urea is normal or decreased. 

The urine in cases of malarial polyuria following estivo- 
autumnal fever generally shows a decreased amount of urea. 

Uric Acid. — Rem-Pici claims that no special law controls the 
excretion of uric acid during the febrile attack. The amount is, 
however, as a rule, slightly increased in the estivo-autumnal 
fevers. 

Chlorides. — The chlorides are not appreciably increased as a 
whole; but, during the first part of the estivo-autumnal attacks, 
they are increased during the intermissions of the fever, falling 



88 ESTIVO- AUTUMNAL MA LABIA 

during the febrile stage. In the polyuria following the estivo - 
autumnal fevers the increase in phosphates is marked. 

Sodium and Potassium. — Rem-Pici found that in the estivo - 
autumnal malarial fevers, one -half of his cases showed dimin- 
ished sodium and potassium during pyrexia, while the other half 
showed the diminution during apyrexia; more sodium was elimi- 
nated during the pyrexia in one -half, while in the other half 
more sodium was eliminated during apyrexia. 

Iron. — Colasanti and Jacoangeli have demonstrated that more 
iron is present in the urine of malarial patients than that of 
other fevers, and is greater after than during the attack. It is 
greatest in the most severe infections. 

Albumen. — In the majority of severe estivo- autumnal fevers 
albumen is present in greater or less amount in the urine, and 
is usually associated with hyaline or granular casts. All fatal 
cases of pernicious estivo -autumnal fever show albuminous urine 
prior to death. This subject will be further discussed in the 
chapter upon complications. 

Indican. — From personal observation I believe that the amount 
of indican is almost invariably increased in the urine of patients 
suffering from the estivo -autumnal fevers. 

Etiology of the Fever. — In the regularly intermittent 
malarial fevers it is well known that the onset of the fevers is 
coincident with the segmentation of a group of parasites. The 
same is true in the estivo- autumnal fevers, although the segmen- 
tation of the parasites is not so easily observed, especially in the 
peripheral blood. Blood from the spleen, however, will also show 
a preponderance of segmenting forms, at the onset of the fevers, 
and, as I have shown, this occurs almost as regularly in estivo- 
autumnal fevers as in the tertian and quartan types of malaria. 

To what is the fever due ? Many and various have been the 
theories which have from time to time held the attention of 
scientists regarding this question. Laveran believed that the 
febrile attack is due to nerve-irritation; Richard, that it is the 
index of the reaction of the human organism to the malarial 
parasites; Golgi, that the febrile paroxysm is due to the invasion 
of fresh red blood - corpuscles by the young parasites, while 
Antolisei concluded that the invasion of the red cells by the 
parasites had little to do with the rise of temperature, which he 
believed to be due to the setting free in the blood -plasma of 
the newly-born parasites. 



ETIOLOGY OF THE FEVEB 89 

To Baccelli,* however, we owe the most reasonable theory 
of the rise of temperature in malaria, and the one which is 
to-day accepted by most authorities. He suggested that during 
segmentation and the entrance of the young parasites into the 
blood, certain toxic products were liberated, which produced the 
fever. These toxic products he considered to be chemical poisons 
of unknown nature, formed during the development of the 
parasites within the red blood -corpuscles and liberated during 
sporulation. This theory has been accepted by Marchiafava, 
Bignami, Mannaberg, Golgi, Thayer, and others. I believe that 
this theory explains most fully the rise of temperature in 
malarial fevers, and, reasoning from analogy, that it is without 
doubt correct. From our knowledge of other infectious diseases, 
it is impossible to believe otherwise than that the fever of 
malaria is due to the liberation of toxic products in the blood 
during the segmentation of the parasites. 

While we must admit that there is no absolute proof that 
this is so, yet there have been certain facts ascertained which 
go far toward establishing the theory upon experimental evi- 
dence. Queirolo has found that the perspiration from patients 
suffering from malarial fever, and collected during the paroxysm, 
was very toxic to guinea pigs, while the perspiration from 
normal individuals was not. This would tend to prove that 
there were toxic substances liberated. 

The researches of Flexnerf have furnished almost conclusive 
proof of the truth of Baccelli's theory. He has described necrotic 
areas in the organs of malarial patients, focal in character, and 
similar to those described by other authorities in diphtheria, 
typhoid fever, measles, scarlet fever, etc., and which are, with- 
out doubt, due to toxic substances circulating in the blood. 

In the light of our present knowledge it is probable that the 
rise of temperature in all malarial fevers is due to toxic substances 
liberated by the parasites during sporulation. The toxic matters 
found by the breaking down of the red blood -corpuscles has, I 
believe, but little to do with the rise of temperature. 

The periodicity of the rise in temperature is easily explained 
by the periods of time elapsing between the sporulation of the 
parasites, and in the cases of continued fever, by the fact that 
multiple groups of parasites are present which sporulate at short 

*"Deutch. med. Woch.," Aug. 11, 1890. No. 32. 
t "Journal of Experimental Medicine," 1897. 



90 ESTIVO -AUTUMNAL MALARIA 

intervals, thus causing an almost constant discharge of toxic 
matter into the circulation. 

The question arises: How can the cases of sometimes perni- 
cious malarial fever which occur without a rise of temperature 
be explained ? Such cases undoubtedly occur, and I have myself 
observed a fatal case in which the temperature throughout the 
disease was normal or subnormal, yet in which the blood from 
the spleen showed numbers of sporulating estivo- autumnal para- 
sites. As in other diseases, so in malarial fevers, many excep- 
tions are noted to the general rule, and idiosyncrasies occur which 
cannot be explained. In such cases there is probably present 
some organismal peculiarity which prevents a rise of temperature, 
which we, as yet, know nothing of. 

After an estivo -autumnal fever has persisted for some time, 
it will sometimes be noted that the fever disappears entirely or 
becomes modified, even though the parasites are still undergoing 
sporulation. While we cannot absolutely state the reason for 
such disappearance of the fever, it is probable that the continued 
action of the toxic substances upon the organism has resulted in 
its acquiring a relative immunity to the fever -producing toxin, 
or, perhaps, has stimulated the production of antitoxic sub- 
stances. 



CHAPTER XI 

SPECIAL PATHOLOGY OF THE ESTIYO- AUTUMNAL FEVERS— ACUTE 
INFECTIONS 

The pathological changes occurring in the viscera are similar 
in infections with both the quotidian and tertian estivo- autumnal 
parasites, and in describing them I shall not undertake to differ- 
entiate between them. 

Among those who have contributed very valuable studies upon 
the special pathology of malaria may be mentioned Bignami, Gua- 
ruieri, Laveran, Councilman and Abbott, Bastianelli, Dock, Barker, 
Monti, and Thayer. In recent years our knowledge of the changes 
occurring in the organs in malarial infection has been greatly added 
to by such researches, and we have come to understand better the 
extensive pathological ravages of such infections. I cannot 
better introduce this portion of our subject than quote Marchia- 
fava and Bignami' s* admirable remarks concerning the pathology 
of malaria. They say: "The malarial infection develops in the 
blood; here only, and chiefly within the red corpuscles, can the 
parasite live. From this it follows that the parasite invades the 
red corpuscles, and nourishes itself at their expense, transforming 
the coloring matter of the corpuscles into black pigment (which, 
after the multiplication of the destruction of the parasite, is in- 
corporated into the white, cells) or otherwise injuring the red 
corpuscles. In consequence of this infection of the blood, we 
find, in addition to the destruction of the cells, a production of 
the detritus of the red corpuscles and of the parasites, the pres- 
ence of pigmented white cells, and the penetration of erythro- 
cytes containing parasites and of leucocytes containing pigment 
into the capillaries of all the organs. It can be understood from 
this primary localization of the infection how the principal changes 
must be found in the hematopoietic organs in addition to the 
blood, and how alterations are to be encountered in all the 
organs and in all the tissues." This brief summary furnishes 
the key to the pathology of malaria. 

*" Malaria, Twentieth Century Practice," Vol. XIX, p. 227. 
(91) 



92 ESTIVO- AUTUMNAL MALARIA 

SPECIAL PATHOLOGY OF ACUTE ESTIVO -AUTUMNAL MALAKIAL 
FEVEK (PERNICIOUS MALARIAL FEVER ) 

Appearance op Cadaver. — The skin has a peculiar dusky 
brown or grayish hue, more pronounced the longer the infection 
has lasted. The wasting of the tissues depends upon the dura- 
tion of the disease. Rigor mortis is generally only moderate in 
extent. Post-mortem discoloration occurs early and may be in- 
tense. Often a patient dead of pernicious malarial fever will re- 
semble very markedly a yellow fever cadaver externally. 

The Brain. — In no organ are the pathological changes more 
exquisitely illustrated than in the brain, especially in those cases 
which have exhibited cerebral symptoms before death. In rare 
cases the brain will appear almost normal. 

Externally the blood-vessels are generally congested, and the 
entire organ appears hyperemic. Small capillary hemorrhages 
are often observed and edema is often present. Where there 
have been no cerebral symptoms during life, the brain externally 
shows little hyperemia. 

Upon section the cut surface is hyperemic, and small hemor- 
rhages may be present in the substance. The lateral ventricles 
are dilated and filled with fluid, and the choroid plexus is 
markedly congested. The cortex, as a rule, is of a brownish or 
chocolate color, due to melanosis, and often the gray matter is 
more or less pigmented. Small hemorrhages are often found in 
the white substance and also in the cerebellum. In not a few 
cases of pernicious malaria the brain is anemic and no melanosis 
is present. 

Microscopical Examination. — The most advantageous method 
of studying the microscopical changes in the brain is to harden 
small pieces in alcohol and section them, staining with eosin and 
methylene blue or Chenzinski's solution. In making such sec- 
tions, portions should be taken from both the cortex and medulla 
of the brain. The pathological changes present are to be seen 
in the capillaries and in the cells of the brain. 

Appearances Observed in the Capillaries. — As a rule, the cap- 
illaries are filled with blood -corpuscles, most of which contain 
parasites. These parasites may be observed in various stages of 
development or, which is very common, all of them are in about 
the same stage of development. If the parasites contain much 
pigment, the brain appears greatly pigmented, while the reverse 



CHANGES IN NERVE CELLS 93 

is also true. The parasites may be so numerous that there are 
hardly any uninvaded corpuscles seen, or they may be very few 
in number. They are sometimes so numerous as to entirely 
occlude the lumen of the capillaries, thus forming thrombi. The 
small arteries and veins are less rich in infected corpuscles. In 
rare cases the entire cycle of existence of the parasite can be 
found illustrated in one capillary. Besides infected blood -cor- 
puscles, the following structures may be observed in the capil- 
laries : 

a. Free parasites. 

I. Macrophages. 

c. Free pigment. 

d. Pigmented leucocytes. 

e. Endothelial cells. 

a. Free parasites: In some cases large numbers of extra- 
cellular or free parasites, always pigmented, are observed in the 
capillaries. These parasites are always round, oval, or segment- 
ing bodies, with pigment in the form of a solid, minute block, 
situated at or near their center. They are most numerous in 
cases dying of tertian estivo- autumnal fever. 

b. Macrophages: Immense white blood -corpuscles containing 
free pigment and parasites are often seen, often so large as to 
distend and entirely block the capillary in which they are situ- 
ated. These cells may be of endothelial origin. 

c. Free pigment is present in the capillaries, and sometimes 
in immense quantities, blocking up the capillaries and forming 
thrombi. This condition is generally present in cases which 
have presented marked comatose symptoms. 

d. Pigmented leucocytes: Most of the leucocytes present in 
the capillaries are pigmented, and often contain parasites enclosed 
in red corpuscles. The leucocytes are usually few in number. 

e. Endothelial cells: The endothelial cells lining the capil- 
laries are generally swollen and undergoing fatty degeneration; 
they are also pigmented and, by reason of their distension, often 
occlude the lumen of the capillary. They may occur free in the 
capillaries, and often contain parasites. 

Changes in the Nerve -cells. — To Marchiafava and Monti we 
are indebted for valuable contributions upon the changes taking 
place in the nerve-cells as the result of estivo -autumnal malaria. 
These changes occur in both the protoplasm and the nucleus of 
the nerve -cell. In the protoplasm the chromatic bodies of Nissl 



94 ESTIVO- AUTUMNAL MALARIA 

have disappeared, and the protoplasm appears very granular, or, 
in the more grave eases, the protoplasm seems to be disintegrated 
and rarefied. 

The nucleus in such cells may appear normal, or the follow- 
ing changes may be noted, most often in the pyramidal cells: 
The nuclear membrane and nucleolus have disappeared as well 
as the chromatin, or one or the other of these elements may 
persist. 

Notable changes are observed in the branches of the cortical 
cells, consisting of attenuation and nodal formations along them, 
or they present a beaded appearance. Sometimes very large, 
bleb-like swellings occur in their dendrites, connected by very 
slender filaments of protoplasm. 

In rare cases nodes are observed along the axis cylinders. 
All the changes above described are most marked in cases of 
comatose pernicious estivo- autumnal fever. 

The changes in the pia- mater and the spinal cord are the 
same as those described for the brain. 

Changes in the Retina. — Guarnieri has studied the changes 
occurring in the retina in pernicious malaria and finds that they 
consist in hemorrhages and congestion of the blood-vessels with 
parasite -infected red corpuscles, macrophages, pigmented leuco- 
cytes and free pigment, thus leading to impairment of function. 

Changes in the Lungs.— The gross pathology of the lungs 
in cases dying of pernicious estivo -autumnal fever is not char- 
acteristic, there being usually, according to the stage of the 
disease, hypostatic congestion, edema, broncho -pneumonia, or 
areas of hemorrhage present. 

Microscopical Examination. — Sections from the lungs show 
the following changes: The alveolar capillaries are congested and 
often contain large numbers of pigmented, parasite -laden, white 
corpuscles (phagocytes) which are often much degenerated. They 
are most numerous in the arterioles and capillaries. The poly- 
morphonuclear leucocytes are rarely observed. The endothelium 
of the capillaries is often swollen and contains small particles of 
pigment; but this condition is very much less marked than in 
the brain, liver, and spleen. 

When broncho-pneumonia has occurred, the exudation into 
the alveoli is mostly composed of polymorphonuclear leucocytes 
and the alveolar cells, while only in rare instances are pig- 
mented leucocytes or phagocytes observed, though the alveolar 



CHANGES IN THE HEART 95 

capillaries are often crowded with them. Neither is free pigment 
common in this exudation. Marchiafava and Bignami claim 
that this lack of diapedesis of the pigmented leucocytes and 
macrophages is due to the fact that they are degenerated, and 
have lost the power of amoeboid motion, by which they are 
enabled to pass through the capillary wall. 

When pneumonia complicates the estivo-autumnal fevers it 
is, without doubt, due to a double infection by the diplococcus 
of pneumonia and the estivo-autumnal parasite. 

Changes in the Heart. — There is nothing characteristic in 
the changes occurring in the heart. The chambers of the heart, 
especially the right auricle, may contain clots composed of in- 
fected red blood-corpuscles and fibrin, with pigmented leucocytes 
and endothelial elements. 

Changes in the Stomach and Intestines.— Macroscopically 
the only change usually observed is more or less pigmentation, 
the mucous membrane being of a dull slate color. In cases 
dying of the choleraic form of the disease, the changes are more 
marked, consisting of hyperemia, necrosis, and even ulceration 
of the mucous membrane. Peyer's patches, as well as the 
solitary glands, are often greatly swollen. 

Microscopical Examination. — Sections of the stomach and the 
intestines show that the capillaries of the villi, especially, are 
crowded with parasite -infected corpuscles (the parasites in 
various stages of development or all in approximately the same 
stage), free parasites and pigment, phagocytes and endothelial 
elements. These may occlude the capillaries, forming thrombi, 
with resulting necrosis and ulceration of the mucous membrane 
in places. The epithelium lining the mucous membrane is often 
necrotic, and there may be present a very general superficial 
necrosis of the superficial layer of the mucous membrane. All 
the changes > are most marked in choleraic pernicious estivo- 
autumnal malarial fever. 

Changes in the Liver. — Macroscopically the following ap- 
pearances are noted: The organ is generally enlarged, often 
markedly so, and is of a dark slate color externally, if the disease 
has persisted for some time. I have seen cases in which the liver 
appeared almost black in color. The capsule is smooth and the 
liver -substance beneath appears homogeneous. Upon section, the 
cut surface is of a very dark brownish red or a slate color, some- 
times almost black, and is bathed in blood, as the organ is gen- 



96 ESTIVO- AUTUMNAL MALARIA 

erally greatly congested. It is not uncommon to find the surface 
mottled with yellowish spots due to fatty degeneration. The 
consistence of the organ is decreased, as a rule. 

Microscopical Examination. — The changes noted are found in 
the capillaries and in the liver -cells. The capillaries contain 
many large macrophagi, containing much pigment and sometimes 
red blood -corpuscles. The number of parasites present is very 
limited. In the liver occur many macrophagi which seem to 
occlude the lumen of the capillaries in which they lie. The en- 
dothelial cells of the organ are greatly swollen and contain much 
free pigment and degenerated parasites. Free pigment sometimes 
occurs in large clumps within the liver -capillaries. The stellate 
cells of Kupfer are often pigmented. The changes in the liver- 
cells consist of atrophy, fatty degeneration, necrosis, pigmenta- 
tion, and degeneration of the nuclei. The pigmentation present 
in the liver -cells is not due to the malarial pigment, but con- 
sists of golden yellow or brownish granules, refractive and often 
appearing spiked or crenated. These little pigment -granules are 
distributed throughout the protoplasm of the liver -cells, and it 
is undoubtedly derived from degenerated red blood -corpuscles. It 
occurs in other diseases than malaria and is most abundant 
toward the center of the liver -lobules. 

One of the most interesting conditions present in the liver 
are the areas of focal necrosis which are sometimes observed. 
These areas are characterized by accumulations of necrotic liver- 
cells, leucocytes, and proliferating connective tissue-cells, and 
are believed by Flexner to be due to a general intoxication. 

Changes in the Spleen. — Macroscopically, the following 
changes are noted: The organ is always enlarged, sometimes 
enormously so. Externally it is of a dark blue or almost black 
color, the capsule being smooth and stretched tightly. Upon 
section, the cut surface is of a chocolate, slate, or almost black 
color, and the consistence of the organ is very greatly decreased, 
it often being diffluent. The elements of the parenchyma can 
seldom be recognized. 

Microscopical Examination. — As a rule, the pulp is greatly 
congested by multitudes of red blood -corpuscles, most of them 
containing parasites. I have, however, seen cases in which but 
few red blood -corpuscles were demonstrable in the spleen. 

The cells of the splenic pulp are pushed apart by the multi- 
tudes of red corpuscles, which contain parasites in various stages 



CHANGES IN THE KIDNEYS 97 

of development, the pigmented forms and the segmenting bodies 
being most commonly observed. Free parasites are less common 
but by no means rare. In cases where the disease has lasted for 
some days, the crescent forms are found, but never in very large 
numbers. 

Besides the parasite -infected red corpuscles, the sections of 
the spleen show an immense number of phagocytes, consisting 
of small cells, resembling lymphocytes, and very large, often im- 
mense cells, known as macrophages. These large cells are usu- 
ally filled with clumps, granules, or blocks of pigment, red cor- 
puscles containing parasites, free parasites and segmenting bodies, 
degenerated red blood -corpuscles, and the smaller phagocytic cells 
first spoken of. The macrophages often present evidences of 
degeneration, as shown by necrosis of the protoplasm. 

The capillaries of the spleen are crowded with infected cor- 
puscles, while the veins contain many phagocytes. The cells of 
the Malpighian bodies do not become pigmented, but the fibrous 
trabecular are greatly pigmented. Free pigment is present through- 
out the pulp sinuses, lying in large blocks or clumps, or in the 
form of small rods and granules. 

Here, as in the liver, two forms of pigment occur: the dark 
brown, or nearly black, malarial pigment, and the golden yellow 
pigment derived from the degenerated and broken down red 
blood -corpuscles. 

Changes in the Kidneys. — As a rule, the macroscopical ap- 
pearance of the kidneys is normal, but sometimes acute conges- 
tion and pigmentation are present. An acute parenchymatous 
nephritis is by no means rare, accompanied by small hemorrhages 
in the cortex of the organ. 

Microscopical Examination. — The changes observed micro- 
scopically in the kidneys are much less marked than in the other 
viscera, especially the brain, liver, and spleen. 

The Malpighian tufts are often found congested and the seat 
of small capillary hemorrhages. There is but little pigmentation 
generally, but sometimes the glomeruli appear much pigmented. 
The pigment is situated within the leucocytes, the capillaries, and 
in the endothelial and epithelial cells. Parasites, either free or 
within the red corpuscles, may be seen occasionally within the 
glomerular capillaries, but they are few in number. The epithe- 
lium of Bowman's capsule is generally undergoing proliferation, 
and the capsular space may be occluded by fibrinous material. 



98 ESTIVO- AUTUMNAL MALARIA 

The epithelium lining the convoluted tubules is undergoing 
degenerative changes, fatty degeneration, and necrosis. The 
straight tubules often contain hyalin, epithelial, or granular 
casts. The intertubular capillaries are somewhat congested, and 
in them free pigment in small amount is observed, as well as 
endoglobular parasites, pigmented leucocytes, and large macro- 
phages. All these, however, occur in very much smaller numbers 
than in the capillaries of the brain, liver, or spleen. 

Changes in the Bone -marrow. — Macroscopically the bone- 
marrow varies in color according to the length of time the infec- 
tion has existed. In the long bones, in recent cases, the normal 
yellow color of the bone -marrow is found; while if the infection 
has lasted for some time, as weeks or months, the color varies 
from red to dull black. In acute cases the bone -marrow is very 
soft, even diffluent. 

Microscopical Examination. — In sections of bone -marrow the 
following appearances are noted: The capillary vessels contain 
numerous endocorpuscular parasites, in advanced stages of devel- 
opment, sporulating bodies, and, if the infection has persisted 
long enough, crescentic organisms. They also contain numerous 
macrophages, containing granules and clumps of pigment, as well 
as red blood -corpuscles. Numerous free segments are generally 
found in the smaller vessels. Externally to the vessels, in the 
marrow pulp, parasites are found in various stages of develop- 
ment, including crescents. Here are also found large numbers 
of macrophages, many of which are undergoing degenerative 
changes. Nucleated red corpuscles are common, as well as pig- 
mented medullary cells. 

The changes found in the other viscera possess but little 
pathological importance. 

I insert here the autopsy record of a case of pernicious quo- 
tidian estivo- autumnal malarial fever, which well illustrates the 
pathological findings in these fevers. This case had had several 
attacks of the fever before the one which proved fatal : 

AUTOPSY UPON THE BODY OP R. G. CRAWFORD, TEAMSTER 

Died 4:30 a. m., July 21, 1900. Age, 52 years. Clinical Diagnosis: Pernicious 
Quotidian Estivo -autumnal Fever. 

Body that of a man apparently 50 years of age, somewhat 
emaciated. Skin yellowish. Eigor mortis slight. Post-mortem 



POST-MOETJEM FINDINGS 99 

discoloration over dependent portions of body. Finger-nails not 
congested. Pupils irregularly dilated. 

Brain. — Dura mater appears normal. The amount of cerebro- 
spinal fluid is increased. The surface of the cerebrum is pale, 
and upon section the medullary appears hyperemic and the cortex 
is slate -colored. The lateral ventricles are filled with fluid. The 
choroid plexus is not congested. Upon section, the cut surface 
of the cerebellum appears normal, save for congestion. Exter- 
nally, the blood-vessels of the cerebrum are congested. 

Thoracic and Abdominal Cavities. — The subcutaneous fat and 
muscular tissue is normal in amount. The pleural cavities are 
free from fluid. The liver reaches about one centimeter below 
the border of the last rib. The omentum contains a large 
amount of fat, and reaches to a level with the umbilicus. The 
appendix is about three centimeters in length, and lies in the 
right iliac fossa; it is normal in appearance. The bladder is 
dilated. The abdominal aorta shows no evidence of sclerosis. 
The suprarenal glands appear normal. 

Liver. — The liver measures 28x21 centimeters. It is dark in 
color externally. The gall bladder contains a large number of 
gall-stones and inspissated bile. Upon section, the cut surface 
of the liver is slate-colored and the lobules are ill -defined. The 
organ is congested. Weight, 1,640 grams. 

Spleen. — The spleen measures 19x12 centimeters. The organ 
is purplish black in color externally. The capsule is smooth. 
Upon section, the cut surface appears almost black in color, 
with light areas scattered throughout. The consistence of the 
organ is very much diminished, it being almost diffluent. 
Weight, 440 grams. 

Pancreas. — The pancreas measures 22x4% centimeters. Upon 
section, the cut surface appears congested. Weight, 115 grams. 

Left Kidney. — The organ is pale in color. The capsule is 
smooth and slightly adherent. Upon section, the cut surface is 
congested. The cortex and pyramids are distinct, and the cortex 
is above normal in thickness. Weight, 125 grams. 

Bight Kidney. — The organ is somewhat lobulated. The cap- 
sule is slightly adherent; otherwise it resembles the left. 
Weight, 125 grams. 

Lungs. — The lungs are crepitant throughout and appear normal. 

The Pericardial Cavity contains about three centimeters of 
clear straw-colored fluid. 
LofC. 



100 ESTIVO- AUTUMNAL MALARIA 

Heart. — The amount of extra- cardial fat is increased. The 
vessels are congested. Upon section, the ventricles contain 
small clots. The muscular walls are about normal in thickness. 
The valves of the heart are normal, with the exception of the 
middle segment of the pulmonary valve, which contains numer- 
ous small apertures. 

Intestines. — The mucous membrane is congested, otherwise 
they are normal. 

Microscopical Examination. — Liver. — Sections of the liver 
show the pathological lesions of cloudy swelling and the changes 
found in pernicious malarial fever. 

The fibrous tissue in the portal spaces has slightly increased 
in amount, and there are large numbers of connective -tissue 
cells present. All the blood-vessels in the organ are increased 
in thickness. The liver-cells are swollen, smoky, and granular 
in appearance, and in many of them the nucleus has entirely 
disappeared. In others, the nucleus is present and shows ne- 
crotic changes, as evidenced by the pale stain and the granules 
of chromatin, which are widely separated or are collected in 
small clumps. 

The protoplasm of the liver-cells contains much fine yellow 
pigment, which seems to be distributed only in the protoplasm 
and not in the nucleus. 

The intralobular capillaries contain a great deal of black 
pigment, numerous large macrophages and smaller mononuclear 
leucocytes. The pigment which is free in the capillaries is in 
the form of irregular blocks, and none of the yellow pigment 
which is present in the liver-cells is seen in the capillaries. 
The large macrophages which crowd the capillaries contain 
within their protoplasm an immense amount of black pigment, 
evidently derived from broken-down malarial parasites; they 
also contain blood-corpuscles containing parasites, and free 
parasites of the estivo- autumnal variety. The number of par- 
asites present is comparatively small, but the amount of pigment 
present is immense, and in clumps so large that many of the 
capillaries are occluded by it. This is especially noticeable in 
the capillaries near the portal spaces. On account of the small 
caliber of the interlobular capillaries the large macrophages are 
compressed, and they appear often as long, slender, pigment- 
bearing cells. Some of these leucocytes are so large as to 
entirely block the capillaries. The malarial parasites present are 



CHANGES IN THE SPLEEN 101 

small, round, or oval bodies, containing a few small granules or 
grains of pigment, generally collected at the center. These are 
presegmenting parasites. No crescent forms were observed in 
the liver. The stellate cells of the Kupfer contain black pig- 
ment and sometimes small parasites. 

In numerous places throughout the capillaries of the liver 
there are large bleb -like parasites containing pigment, which are 
evidently degenerating. The pigment in the macrophages is in 
the form of small round blocks, or larger irregular collections, 
and is dark brown or almost black in color. There is not a 
single capillary in the section that does not show pigment - 
bearing cells. 

Spleen. — Sections of the spleen show the changes character- 
istic of pernicious malarial fever. 

The Malpighian bodies are somewhat fibrous, and at their 
border there is an immense amount of yellowish black pigment. 
The splenic pulp contains a small number of red corpuscles 
which contain small, round or oval, estivo- autumnal parasites, 
which are pigmented. There is not the usual number of red 
corpuscles present in this spleen that we generally find in 
spleens from cases of pernicious malaria. The splenic pulp also 
contains immense numbers of pigment cells, or macrophages, and 
large masses of free pigment. The macrophages are large white 
cells, which contain the following objects: (1) large, irregular 
collections of brownish black pigment; (2) red corpuscles con- 
taining small, round, pigmented, estivo -autumnal parasites; 
(3) free estivo -autumnal parasites, most of them pigmented and 
showing signs of segmenting; (4) fine granules of a yellowish 
pigment which is entirely distinct from the black pigment present. 

Some of the macrophages show all of these within their pro- 
toplasm, while others, and they in the majority, show only 
one or two free parasites and irregular collections of pigment. 
As a rule, these white cells are about six times the size of a 
blood-corpuscle, but some of them are present which are very 
much larger. These very large cells entirely block the capil- 
laries of the organ, thus hindering the circulation. 

Besides the macrophages, there are numerous mononuclear 
leucocytes and endothelial cells which do not take up the pig- 
ment of the parasites. The polymorphonuclear leucocytes are 
comparatively few in number. Everywhere throughout the sec- 
tion there are very large masses of free pigment situated in the 



102 ESTIVO- AUTUMNAL MALARIA 

spaces of the splenic pulp, often so large as to rupture them 
and cause an area of necrosis in which they are situated. 

Throughout the spleen may be seen crescentic forms of the 
quotidian estivo-autumnal parasite, but they are comparatively 
few in number. These crescents appear exactly as they do in 
the peripheral blood. In the spleen there are also numerous 
large bleb -like parasites, like those seen in the liver, which 
contain much pigment and numerous vacuoles. These are evi- 
dently degenerating bodies. The segmenting forms of the par- 
asite are remarkably few in number in the sections of the 
spleen, but many of the macrophages contain segmenting bodies. 

Kidney. — Sections of the kidney show the pathological lesions 
of acute nephritis and the changes present in pernicious malaria. 
The Malpighian bodies are greatly congested, the capillaries 
being filled with blood and some of them have ruptured, thus 
causing hemorrhages within the tufts. Many of these capillaries 
contain small, free, round or oval parasites, containing a small 
clump of pigment at their center. The capillaries also contain 
a few red cells which are infected by the parasites. There is 
present a small amount of free pigment. 

In the capillaries may be seen, now and then, a large bleb- 
like body, evidently a degenerated parasite, like those seen in the 
liver and spleen. 

The number of infected corpuscles and free parasites, and the 
amount of pigment, is very much smaller than in the case of the 
liver and spleen. No crescent forms were observed in the Mal- 
pighian bodies. 

The epithelium of the tubules is much swollen and is rapidly 
proliferating, while the protoplasm of the cells is ' smoky and 
finely granular in appearance and contains, in many instances, 
pigment -grains of a yellowish color. 

One of the most interesting features of the kidney -sections 
is the occurrence, within many of the tubules, of collections of 
black pigment and here and there a few parasites. There are 
few parasite -infected red blood -corpuscles present in the tubules. 
The capillaries between the tubules contain numerous free para- 
sites, round or oval in shape, and pigmented, also macrophages 
and infected red corpuscles. The macrophages, as in the liver 
and spleen, contain free pigment and parasites, red corpuscles 
containing parasites or yellowish pigment. The walls of the 
capillaries are not thickened. It is especially noticeable how 



CHANGES IN BRAIN 103 

slight the amount of pigment is in the kidney as compared with 
the liver and spleen, and how few parasites are present. 

Brain. — Sections of the brain show the pathological lesions of 
pernicious estivo- autumnal fever of comatose type. The changes 
observed in the sections of the brain may be divided into those 
occurring within the capillaries and those within the brain 
substance proper. The small capillaries of the brain, especially 
those of the cortex, are crowded with pigmented, free parasites, 
leucocytes containing pigment, and in some places by small col- 
lections of yellow pigment. The infected capillaries are most 
numerous in the cortical portion of the brain, but they are by no 
means rare in the medullary portion. The pigment within the 
capillaries is generally collected in irregular masses, is brownish- 
black in color, and, in some places, entirely occludes the lumen 
of the capillary. This condition, which is very noticeable through- 
out the sections, no doubt accounts for the symptoms present, 
referable to the brain. 

The parasites present in the capillaries are mostly free, are 
oval or circular in shape, small, and contain pigment which is 
generally collected near the center, in the form of a small grain 
or collection of grains. It is remarkable how uniform these para- 
sites are in appearance and how rarely is seen a red cell infected 
by parasites. It may be that during the preparation of the speci- 
men the red cells became disintegrated; but this is hardly prob- 
able. In some places the capillaries are occluded by large white 
cells (macrophages) containing much pigment and numerous free 
parasites. Taken as a whole, the amount of pigment present in 
the brain is not large. 

The changes occurring within the substance of the brain con- 
sist in a necrosis of the protoplasm of some of the cells, as is 
evidenced by the irregular staining of the protoplasm and nuclei. 

Sections were not made of the stomach and intestines, as they 
presented no evidences of malarial infection. 



CHAPTER XII 

CUBICAL DESCRIPTION OF IRE ESTIVO- AUTUMBAL FEVERS — 
CLASSIFICATION AND SYMPTOMATOLOGY OF THE TERTIAN 
ABB QUOTIDIAN FORMS— ANALYSIS OF SYMPTOMS A2^D PHYSI- 
CAL EXAMINATION— EXAMINATION OF THE BLOOD 

Classification. — As stated in the opening chapters of this 
work. I hold with Marehiafava and Bignami that there ar 
distinct types : ~:ivo- autumnal malarial fever, both from a 
clinical and etiological standpoint. 

Clinically, all estivo -autumnal fevers should be classed as 
t forms of malarial fever, in contradistinction to the tertian 
and quartan infections, which are classed as mild forms of ma- 
larial fever. This classification of the estivo - autumnal infections 
r- forms is most important. "While, of course, ever; 

such infection does not result fatally, and while most are 
readily amenable to treatment and many are cured spontaneously, 
still the fact remains that almost all the pernicious malarial fc rs 
are caused by the estivo -autumnal parasites, and even- 
showing the presence in the blood of such parasites should be 
I as serious in nature. 

The idea that there is a parasite peculiar to the pernicious 
malarial fevers, which is alone capable of producing them, is one 
which has been long ago exploded and is entirely false. The 
estivo -autumnal parasites occurring in the blood of such 
differ in no way from those occurring in estivo -autumnal fever 
in general, hence the danger that any infection due to these 
parasites may become pernicious or malignant in character. 

As is well known, the estivo -autumnal fevers occur most fre- 
quently, in temperate climates, in the summer and autumn, 
cially during the months of July. August. September an ~ 
but in the tropics, and indeed in subtropical countries, this type 
of infection is present throughout the year and supplies the 
feer part of the malarial fevers of these regions. From this 
:hat the time of the occurrence of these fiev 
purely a geographical proposition. In the United States, for in- 

(104) 



FORMS OF ESTIVO- AUTUMNAL MALARIA 105 

stance, such fevers occur in the summer and autumn, as a rule, 
while in the Philippine Islands they are present throughout the 
year. Relapses of estivo- autumnal fever may, however, occur at 
any time, and a careful distinction should be made, in temperate 
climates, between such relapses and primary attacks. 

It should be distinctly understood that either the tertian or 
quotidian estivo -autumnal parasite is capable of producing per- 
nicious symptoms. As to which is most often associated with 
pernicious malarial fever, I am as yet, from personal observations, 
unable to say. Marchiafava and Bignami have found that in the 
malarial fevers of Italy the tertian estivo -autumnal parasite is 
most often found, whereas I have most often found the quotid- 
ian parasite in cases infected in Cuba and the Philippines. I 
believe that, in all probability, one occurs about as frequently 
as the other, and that it is premature to consider either as peculiar 
to malignant infections. It is probably the susceptibility of the 
patient and the number of parasites present which determines 
the pernicious character of the fever rather than the variety of 
the estivo -autumnal parasite present. 

In previous chapters I have considered the morphological dif- 
ferences between the tertian and quotidian parasites, but we do 
not have to rely only upon such facts, for both varieties of the 
fever are distinct clinically, in uncomplicated cases. I am aware 
that many American observers have failed to distinguish the two 
types of fever which are here described, but I am convinced that 
it has been because of insufficient study of the cases without 
quinine, and also because the most typical cases occur in the 
tropics. 

I feel sure that an unprejudiced observer will admit that 
Marchiafava and Bignami's classification is correct, both from 
an etiological and clinical point of view, if he studies uncompli- 
cated cases of estivo-autumnal malarial fever in which quinine 
has not been recently given. Certainly nothing could be more 
distinct, clinically, than typical cases of tertian and quotidian 
estivo-autumnal malarial fever. 

As to the frequency of the occurrence of the two types of 
fever, it is undoubtedly true that the tertian form is altogether 
the most common. From the data which I possess, comprising 
several hundred cases of estivo-autumnal fever, the tertian par- 
asite was present in about 75 per cent of the cases. 

Before considering the symptomatology of these fevers, the 



106 ESTIVO- AUTUMNAL MALARIA 

impression which prevails among certain physicians, that a 
remittent temperature is characteristic of them, deserves a short 
consideration. In the first place, this impression is a false one. 
Irregularity or remittence is not at all characteristic of the 
estivo- autumnal fevers. These fevers, if uncomplicated, are just 
as regular in their manifestations as either the simple tertian or 
quartan fevers, in the great majority of cases. I am willing to 
admit that irregularities of temperature are more apt to occur 
in estivo -autumnal cases than in tertian or quartan cases, but 
that such irregularities are characteristic of them, I am satisfied 
is untrue. Any malarial fever may become irregular, such 
irregularity being due to a multitude of causes, one of the chief 
of which is the unscientific use of quinine. 

From a consideration of the temperature curves the estivo - 
autumnal fevers may be divided, clinically, as follows: Tertian, 
quotidian, irregular, and remittent or continued. 

Some authorities have striven to establish a class of malarial 
fevers characterized by long intervals between the paroxysms, in 
which six, eight, or even ten days elapse between the attacks of 
fever. Such a classification is a remnant of the "Dark Ages of 
Medicine " and is undeserving of consideration. Such cases are 
simply relapses of a previous malarial infection and are as apt 
to be due to the tertian or quartan parasites as to the estivo- 
autumnal. Now and then a case is observed which apparently 
shows some such irregularity, but it is only apparent, for an 
examination of the blood will demonstrate that the cycle of 
existence of the particular parasite causing it is completed, as 
usual, although the clinical symptoms may be atypical; in other 
words, the infection is latent. 

SYMPTOMATOLOGY OF THE ESTIVO- AUTUMNAL MALARIAL FEVEKS 

In considering this portion of our subject, I shall divide it, 
from a clinical point of view, as follows: 

1. The Tertian Estivo-autumnal Fever. 

2. The Quotidian Estivo-autumnal Fever. ' 

3. Pernicious Estivo-autumnal Fever. 

4. Latent or Masked Estivo-autumnal Fever. 

Tertian Estivo-autumnal Fever. — A patient suffering from 
this form of estivo-autumnal fever presents, as a rule, the fol- 
lowing symptoms: 



SYMPTOMS DURING PAROXYSM 107 

Prodromal. — The prodromal symptoms are loss of appetite, 
slight headache, more or less dull pain in the back and legs, 
frequent urination, nervousness, and a general feeling of "un- 
wellness" and malaise. 

Symptoms During the Paroxysm. — As a rule three stages may 
be distinguished in the paroxysm. 

The Cold Stage. — This is generally initiated by yawning and 
a feeling of weakness and slight headache. In the majority of 
cases there is no distinct chill, but chilly sensations are most 
often noticed along the spinal column, consisting of evanescent 
" creeping " sensations . 

At the same time, marked malaise develops, sometimes very 
extreme, together with nausea and vomiting in some cases; the 
headache increases and the patient is mentally depressed. The 
skin presents the well-known appearance of ""goose flesh," and 
it and the mucous membranes are cyanosed; the extremities are 
cold and feel heavy to the patient. The legs and back ache, the 
pain being greatest in the lumbar region; the tongue is broad 
and flabby, and heavily coated; the respirations rapid, and the 
pulse is weak, rapid, and often irregular. As a rule, the cold 
stage does not last more than half an hour, and the patient sel- 
dom shakes with the chill, as in the simple tertian. The tem- 
perature is elevated. 

The Hot Stage. — Gradually the patient experiences a sensation 
of heat, coming first as localized flushings, but soon becoming 
general. The eyes are suffused and brilliant, the face red, the 
entire skin dry and hot. The pulse is rapid and dicrotic, the 
respiration hurried and apparently somewhat difficult; the head- 
ache is intense, and there is either great mental depression or 
nervous excitement; the pain in the back and limbs increases and 
is often almost agonizing. The temperature is elevated, and the 
curve is very characteristic; the nausea continues and vomiting 
may occur repeatedly; diarrhoea may occur, and polyuria is not 
uncommon. This stage lasts for several hours and is succeeded 
by the 

Stage of Remission. — During this stage the symptoms become 
milder and gradually disappear; the temperature becomes normal 
or subnormal, and slight sweating occurs, as a rule. Headache 
often remains during the intermission. 

As a rule, attacks of tertian estivo- autumnal malaria occur 
toward evening, extend throughout the next day, and subside 



108 ESTIVO- AUTUMNAL MALAEIA 

during the first hours of the third day, the paroxysm thus lasting 
thirty-six hours or more, and recurring every forty-eight hours. 

Quotidian Estivo- autumnal Fever. — Prodromal Symptoms. 
— The prodromal symptoms are the same as those observed in the 
tertian form of the fever. 

Symptoms During the Paroxysm. — As in the tertian form, the 
three stages described may generally be observed, but in this 
form a distinct chill is much more commonly observed, the pa- 
tient often shaking with it. The other symptoms are essentially 
the same, save that the temperature curve is not so characteristic. 
The attacks most often occur toward evening and recur every 
twenty -four hours. 

ANALYSIS OF THE SYMPTOMS OF THE TEKTIAN AND QUO- 
TIDIAN FOKMS OF ESTIVO -AUTUMNAL MALAEIAL FEVEK 

Temperature Curve in Tertian Estivo - Autumnal Fever. — In 
uncomplicated cases of tertian estivo -autumnal fever, in which 
no quinine has been given for the first three days, the tempera- 
ture curve is absolutely typical and a diagnosis could be arrived 
at from it alone, for in no other disease is such a temperature 
exhibited. The onset of the fever is abrupt, there being a sud- 
den rise of temperature to 103° or 104° F. as a rule; following 
this there occur slight oscillations in the temperature, covering 
several hours, in which the temperature falls from one -half to 
one degree; this period of oscillation in the temperature curve 
is followed by a distinct fall or pseudo- crisis, in which the tem- 
perature drops from one and one -half to two, or even three, de- 
grees. This fall in the temperature is often so extreme that one 
receives the impression that it is the real crisis; on the contrary, 
however, the fever again rises to a higher point than it had 
before attained, and then follows the true crisis, in which the 
temperature falls generally below normal. From this it will be 
seen that the temperature curve may be divided into five stages : 
1, the initial rise; 2, the period of slight remissions or oscilla- 
tions; 3, the pseudo -crisis; 4, the precritical rise; 5, the true 
crisis. This typical temperature curve is well illustrated in Chart 
No. 1. 

As will be seen, the fever lasts for many hours, generally 
over twenty-four, and often from thirty-eight to forty. That is 
to say, the paroxysms really cover two days, but as the initial 



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THE TEMPERATURE CURVE 111 

rise occurs every third day, the fever is essentially tertian in 
character. It differs markedly from the simple tertian as regards 
the temperature curve, that of the simple tertian only resembling 
it when a double tertian infection occurs in which the two 
groups of parasites mature within a few hours of one another, 
thus causing a more or less continuous fever. In the estivo- 
autumnal tertian there is no day in which fever is absent; 
whereas in the simple tertian, the day intervening between the 
paroxysms is free from fever. 

In a large proportion of cases of tertian estivo-autumnal 
fever, the characteristic temperature curve described will be 
exhibited; but there are many deviations from the classical 
type. These deviations are due to several factors, among the 
most important of which are the following: improper medication 
with quinine; double infections or infections with more than 
one variety of the malarial parasite; anticipation of the attacks, 
especially common in the pernicious fevers; retardation of the 
attacks; slight elevations of temperature between the attacks, 
and complication with some other disease. 

The most beautifully typical tertian estivo-autumnal temper- 
ature curve may be rendered atypical and very confusing by the 
administration of small doses of quinine at irregular intervals; 
and this is one of the greatest stumbling blocks in the way of 
a correct clinical diagnosis of the disease. 

The chief alterations in the temperature curve produced by 
these various factors are: 

1. A curve almost identical with that of a simple tertian, 
produced by the short duration of the paroxysm. (Chart No. 2.) 

2. A curve characterized by a long period of slight remis- 
sions, due to prolongation of the paroxysm. (Chart No. 3.) 

3. A curve showing no well-marked initial elevation of 
temperature, thus causing a more or less continuous fever line. 

4. A continuous curve showing only slight remissions, due to 
overlapping of the paroxysms. (Chart No. 4.) 

5. A curve showing a very marked pseudo- crisis, thus caus- 
ing the fever-line to resemble that of a double tertian or quo- 
tidian estivo-autumnal infection. 

6. A curve in which the five stages described are reversed. 
Besides these modifications there occur many which are so 

complex that it is impossible to recognize with what disease we 
are dealing without an examination of the blood by the micro- 



112 ESTIVO- AUTUMNAL MALARIA 

scope. Such complex temperature curves are most often due to 
the administration of quinine in an improper manner. 

It may be well to state here that a chart which shows only 
the morning and evening temperature is far worse than useless 
in tertian or quotidian estivo - autumnal fever, and should be 
carefully guarded against. The temperature should be taken at 
least every four hours, and to secure the most typical charts it 
should be taken every three hours. In these cases a morning 
and evening chart is inexcusable. 

Temperature Curve in Quotidian Estivo -autumnal Fever. — In 
the quotidian form of the disease the temperature curve is not 
very characteristic. It consists essentially in an abrupt rise of 
temperature to 103° F. or above, succeeded by as abrupt a fall, 
the entire attack lasting, as a rule about eight hours, but some- 
times longer, while in the typical form the temperature, during 
the crisis, generally falls below normal. This is a very marked 
peculiarity of the quotidian form, the temperature almost inva- 
riably falling below normal, quite often to 95° F., and some 
times below. (Chart No. 5.) In no other disease does the tem- 
perature fall so far below the normal without a fatal result to the 
patient. 

The temperature curve in the quotidian form seldom remains 
regular for long at a time, as the attacks tend to run into one 
another, thus giving rise to a more or less continuous fever. 
This is especially true in those cases assuming a pernicious type, 
but not in all such cases, for I have seen fatal cases in which the 
temperature curve remained very regular. 

As will be seen, the curve in the quotidian form of estivo- 
autumnal fever is not very characteristic, resembling very closely 
that of an ordinary double tertian infection, and we must, there- 
fore, depend upon the microscope in making our diagnosis. There 
is no greater proof of the value of a microscopical examination of 
the blood than is found in the ease with which the various forms 
of malarial fever are diagnosed and differentiated by it, and such 
an examination is often instrumental in saving life. 

The Chills. — As a rule, in the estivo - autumnal malarial 
fevers, in contradistinction to the tertian and quartan fevers, the 
chill is slight or almost absent. In the majority of cases the pa- 
tients simply complain, of chilly sensations along the spinal col- 
umn, and seldom shake severely. This is especially true of the 
tertian infections. In the quotidian form the chill is generally 







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THE SWEATING 115 

present and more pronounced, and in both occur cases in which 
the chill is very severe and exhausting. There are also many- 
cases in which the chill is absent or so slight as not to attract 
the attention of the patient. As a rule, the chilly sensations, 
or the chill, do not last over three-quarters of an hour, at the 
longest, and often not over ten or fifteen minutes. 

The Sweating. — In the tertian estivo- autumnal fever the 
sweating is not excessive, and is often so slight as not to attract 
attention. In the quotidian form the sweating is generally more 
severe, but not, as a rule, so marked as in the simple tertian or 
quartan malarial fevers. In both forms, however, the sweating 
stage may be prolonged and exhausting, the amount of perspi- 
ration being excessive. 

Facial Appearance. — In primary acute attacks, both of the 
tertian and quotidian estivo -autumnal fevers, the face is flushed 
or congested, the eyes brilliant, the conjunctivae congested. An 
anxious expression is often present, and the patient looks very 
sick. Exceptions to this rule are noted in which the face is 
pale and the patient appears indifferent or even cheerful. In 
cases which have suffered from relapses the face is usually brown- 
ish yellow in color, slightly flushed and haggard -appearing. 

The SMn. — In primary acute attacks of both forms of these 
fevers the skin usually appears normal in color, but where re- 
lapses have occurred it usually has a brownish yellow, anemic 
appearance. During the fever certain eruptions, or rashes, may 
appear upon the skin, especially urticarial eruptions, which I 
have observed very often. 

Peeling of the shin is sometimes observed, occurring toward 
the latter part of an acute attack. I remember such a case, in 
which the peeling was very extensive, portions of the epidermis 
several centimeters in diameter separating. 

One of the most frequent conditions present in both these 
forms of estivo -autumnal fever is herpes of the lips. This oc- 
curs in quite a large proportion of the cases. Herpes of the 
nose is also common. In several cases I have observed herpes 
of the penis occurring with or immediately after a paroxysm. 

The Mouth and Tongue. — The mouth, during the paroxysms, 
is dry, the tongue thickly coated with a dirty white or brownish 
fur, and either broad and flat or pointed and narrow. In severe 
cases the tongue is dry and coated with a thick brown fur, and in 
pernicious cases sordes may form upon the teeth as in typhoid. 



116 ESTIVO- AUTUMNAL MALARIA 

Symptoms Connected with the Circulatory System. — 
The heart -sounds are generally clear, but often a slight systolic 
souffle may be heard. In many cases, however, the heart- 
sounds are muffled or the second sound is increased in volume. 

The pulse is weak and rapid; it is easily compressible and 
remarkably dicrotic in the majority of cases. In not a few eases 
it will be found intermittent, and sometimes alarmingly irregular. 
In many cases the patient complains of a dull or acute pain 
over the heart, which is in all probability neuralgic in char- 
acter. The area of heart-dullness is not altered in uncomplicated 
cases. 

Symptoms Connected with the Respiratory System. — 
The respirations, in an acute attack of these fevers, are always 
quickened and often appear to be slightly labored. This is due 
to the greater or lesser amount of congestion present in the 
lungs and the high fever. A slight cough is a very frequent 
symptom. 

Physical examination of the lungs may show slight areas of 
lessened resonance and rales, chiefly sibilant in character. Moist 
rales are sometimes heard. A mild catarrhal bronchitis is of 
frequent occurrence. 

Symptoms Connected with the Digestive System. — Nausea 
is a very common symptom, occurring in about 90 per cent of 
all cases, and is often very distressing and exhausting. 

Vomiting occurs in a large proportion of the cases, and some- 
times is so severe and persistent as to endanger the patient's life. 

Pain over the stomach is a common symptom and may be 
agonizing in character. Loss of appetite and loathing of food 
are common symptoms during the paroxysms. Pain over the 
abdomen is sometimes complained of, and may be so severe as 
to simulate peritonitis. In rare cases it may be localized in the 
region of the appendix, and simulate appendicitis. 

Diarrhoea is a common symptom, occurring during the par- 
oxysm as a rule. 

Constipation is not rare during the early portion of an attack. 

Symptoms Connected with the Glandular System. — En- 
largement of the spleen is almost invariably present, the organ 
being plainly palpable and often extending very nearly to the 
umbilicus, or beyond it. In recent infections it is soft and 
rounded, and very tender upon pressure, while in old infections 
it is hard, and presents a well-defined, rather sharp margin. 



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118 ESTIVO- AUTUMNAL MALARIA 

The liver is often enlarged and tender, especially in cases 
which have often suffered from relapses. 

Symptoms Connected with the Urinary System. — In many- 
cases a polyuria exists before, during, or after a paroxysm. 

Pain over the kidneys is a very common symptom, but it is 
doubtful whether it is referable to these organs. 

Albuminuria is rather common, and will be discussed in the 
chapter upon complications. 

Symptoms Connected with the Nervous System. — Delirium 
occurs in a fairly large percentage of the cases, and is usually of 
a mild type; active maniacal delirium is sometimes observed. 

Stupor is a common accompaniment of the more severe forms 
of estivo -autumnal fever. 

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serious import. 

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to the forehead and occiput, and is often almost unbearable. 
It persists, as a rule, throughout the paroxysm, and often in the 
interval. 

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are very annoying. 

Tain in the back and limbs is always present and is generally 
one of the hardest things which the patient is called upon to 
bear. The pain is usually of a dull aching character, but may 
be sharp and radiating. Patients suffering from either the 
tertian or quotidian forms of estivo -autumnal fever are often 
extremely nervous, both during and between the paroxysms, 
and this condition not very rarely deepens into a mild form of 
melancholia; such cases should be carefully watched, as suicidal 
tendencies are apt to develop. 

In closing this summary of the symptomatology of the estivo- 
autumnal fevers, it is but proper to say that many cases will pre- 
sent but a few of these symptoms, while others will present 
nearly all of them; no hard and fast rule can be laid down re- 
garding the symptomatology of these forms of malaria. Many 
will resemble typhoid fever in their course and symptoms, and in 
such cases we must depend upon the microscope in making our 
diagnosis; others will resemble nothing "in the heavens above 
or in the earth beneath," and here again the microscope will be 
of inestimable value; there will be others so typical that "he who 



PHASES OF PARASITE IN BLOOD 119 

runs may read," but even in these the use of the microscope 
should never be neglected, for the examination of the blood is 
always essential in making a scientific diagnosis. 

Examination of the Blood During the Clinical Periods 
op the Disease. — For convenience I have tabulated below the 
various phases of the tertian and quotidian estivo- autumnal para- 
sites visible in the blood at various periods of the infection. 

The Tertian Estivo -autumnal Parasite. — 1. During the febrile 
period the small, more or less amoeboid, hyalin, intracorpuscular 
parasites are observed, from one -tenth to one-sixth the size of 
the red corpuscle. 

2. During the afebrile stage the young pigmented forms are 
found in the blood. 

3. Before the onset of a paroxysm, the pigmented forms are 
more numerous and have attained their largest size, about one- 
fourth of the infected corpuscle. 

4. At the commencement of a paroxysm the parasites are 
generally remarkably few in number in the peripheral blood, 
but the young, unpigmented forms appear about the acme of 
the fever. 

The Quotidian Estivo -autumnal Parasite. — The examination of 
the blood in the quotidian cases gives results substantially the 
same as those obtained in the tertian infections as given above, 
so far as the time of appearance of the parasites in the pe- 
ripheral blood is concerned, so that it is unnecessary to repeat 
the data given. 

In the irregular forms of estivo-autumnal fever it is often 
impossible to follow accurately the life -cycle of the parasites in 
the peripheral blood. Many of these forms are due to infections 
with more than one generation of parasites or double infections 
with the quotidian and tertian parasites or the benign tertian, 
and examination of the blood will, of course, be less satisfactory, 
as regards regularity in the presence of the organisms. 



CHAPTER XIII 

CLINICAL ILLUSTRATIONS OF THE QUOTIDIAN AND TERTIAN 
ESTIVO- AUTUMNAL FEVERS 

In the following chapter I have selected for description a 
number of typical cases of quotidian and tertian estivo-autum- 
nal malarial fever which I have observed in soldiers return- 
ing from Cuba. I have selected these cases from hundreds of 
malarial patients because they were studied for several days 
before quinine was administered, and thus all the typical phe- 
nomena of the paroxysm were exhibited. From the charts shown 
it will be seen how the estivo- autumnal cases conformed to one 
of two types of fever, quotidian or tertian. In a previous con- 
tribution* I have shown how the estivo -autumnal malarial fevers 
present either quotidian or tertian paroxysms, and that each form 
is due to a distinct and characteristic form of malarial parasite. 
My observations confirm those of Marchiafava and Bignami, who 
were the first to describe the forms of the malarial parasites men- 
tioned. They gave the names quotidian and malignant tertian 
estivo -autumnal parasites to the organisms described ; but it 
would seem to be preferable to simply designate them as the 
quotidian and tertian parasites, as, in reality, the term "malig- 
nant" belongs rather to the quotidian than to the tertian 
form, as nearly all the pernicious cases of malaria which I have 
observed have been infected with the quotidian estivo -autumnal 
parasite. 

I hope by the cases adduced to show the value of a careful 
study of our cases of malarial fever, both clinically and micro- 
scopically, and to demonstrate the occurrence of the two forms 
of the estivo -autumnal fever mentioned. I shall consider each 
case separately, giving the clinical history and describing the 
parasites found in the blood. 

The cases are arranged as follows : 

1. Cases of Quotidian Estivo -autumnal Fever. 

2. Cases of Tertian Estivo -autumnal Fever. 

*" Philadelphia Medical Journal," April 7, 1900. 
(120) 



TYPICAL CASES 121 

In considering the subject in this manner, I have aimed to 
give the salient features, both clinical and microscopical, found 
in typical cases; but it should be understood that many cases 
occur which are , not typical, where the temperature curve is 
more or less continuous; cases where there are mixed infections 
or infections with multiple groups of parasites, which it is im- 
possible to describe in the limits of a chapter such as this. In 
such cases the clinical symptoms are often atypical and the 
temperature curves are most irregular and confusing. But no 
matter how typical a case of estivo- autumnal malaria we may 
have, it can be easily made atypical by the administration of 
small, broken doses of quinine. Such treatment — far too com- 
mon — will cause the most typical temperature curve, whether 
quotidian or tertian, to become irregular and often altogether 
unrecognizable as one of malaria, and is the most prolific source 
of the existing confusion regarding the forms of estivo -autumnal 
fever. In combined infections with both the quotidian and ter- 
tian estivo -autumnal parasites, a more or less continued or 
slightly remittent temperature curve is seen, while in cases in 
which quinine in unsuitable doses, at irregular intervals, has 
been given, an irregular, intermittent temperature curve is most 
common. Where, however, no combination of the two varieties 
of the parasites exists, and quinine is not administered, it will 
almost invariably be found that either a quotidian or a peculiar 
tertian temperature curve will be observed. 

CASES OF QUOTIDIAN ESTIVO-AUTUMNAL FEVEK 

There is nothing very peculiar about the temperature curve 
in this form of malarial fever, it very closely resembling an 
ordinary double tertian curve. It is a notable fact, however, 
that most cases of pernicious malarial fever which I have ob- 
served have presented this type of temperature curve, and the 
blood has shown the characteristic quotidian estivo -autumnal 
organisms. None of the cases described in this chapter were 
pernicious in character, as I have purposely selected those of 
a milder type, because they are so much more common. 

Case 1: Chart 6 — Hamilton. — The patient, a soldier, ar- 
rived at Santiago during August, 1898. He was there about 
one month when he was attacked by measles, which was followed 



122 ESTIVO- AUTUMNAL MALARIA 

by dj'sentery. About the middle of October he began to have 
chills and fever. His chills occurred, as a rule, every day, but 
were sometimes irregular. Besides the chills, he suffered from 
nausea, vomiting, very severe headache and diarrhoea. Has had 
several attacks, followed by apparent recovery under treatment. 
He was feeling well on his arrival at the hospital, on June 23, 
1899. Upon the 26th he began to run a temperature character- 
ized by quotidian paroxysms, but had no distinct chill until the 
30th. Up to the latter date he suffered from nausea, some head- 
ache and general pains. On the 30th he had a distinct chill, 
suffered from nausea, vomiting, sweating, severe frontal headache 
and general pain, especially severe between the shoulders. His 
bowels were constipated. 

Physical Examination. — Patient is anemic and emaciated. 
Skin slightly yellow; face flushed; tongue heavily coated with a 
thick, yellowish fur and flabby; lungs and heart normal; pulse 
full and bounding; spleen enlarged and tender, reaching about 
4 centimeters below ribs; liver normal. Some tenderness over 
abdomen on deep pressure, probably due to pressure on spleen. 

Examination of the Blood. — The blood was examined daily at 
intervals until the parasites disappeared. It was found that they 
were the most numerous in the peripheral blood during or just 
after a paroxysm, but at no time were they numerous enough to 
show more than one infected corpuscle, on the average, to the 
field. The parasites were typical of the quotidian estivo- autumnal 
variety, and two forms were observed in the blood: the ring- 
forms and the pigmented forms. The ring-forms were very small, 
indistinct in outline, perfectly circular when at rest, and very 
actively amoeboid. They never showed any signet -ring appear- 
ance, and were never more than one -sixth the size of the infected 
corpuscle. Some infected corpuscles contained two and a few 
even three parasites. The pigmented forms were about one-fourth 
the size of the infected corpuscle, which was always shrunken, 
brassy green in color, and generally crenated. The outline of 
the organisms was much more sharply defined than it was in 
the case of ring-forms, and they were perfectly circular in shape, 
amoeboid motion having entirely disappeared. The pigment was 
in the form of one, or, at most, two rather large, almost black 
dots, either centrally or peripherally situated. The pigment was 
always entirely motionless. No segmenting forms nor crescents 
were observed in this case. The parasites disappeared from the 



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EXAMINATION OF BLOOD 125 

blood two days after the commencement of the administration of 
quinine. 

Treatment. — Quinine, in doses of .36, every four hours. 

On reference to the temperature chart, it will be seen 
that there is nothing very distinctive about the temperature 
curve, beyond its quotidian character and the fact that during 
the first three paroxysms the patient felt slightly chilly, during 
the fourth even the chilly sensations were absent, and that the 
first distinct chill occurred during the fifth paroxysm. As far 
as the temperature curve is concerned, it might very well be 
that of a double tertian, the microscope alone being serviceable 
in differentiating the type of infection present. The temperature 
reached normal after two days' treatment with quinine. The 
subnormal temperature on the 29th, of 95.4° F., is worthy of 
notice, as it has been my experience that in no disease does the 
temperature so often reach low subnormal points as in the 
estivo- autumnal fevers. 

Case II: Chart 7— S. F. Shelton. — The patient, a soldier, 
suffered for several weeks in Santiago, Cuba, from attacks of 
fever, accompanied by chilly sensations, headache, backache, 
slight nausea, and sweating. He grew gradually weaker and 
was tranf erred to the United States, arriving at the hospital on 
January 23, 1899. His temperature remained normal until the 
26th, when he had a chill, which was repeated every day for 
four days. He suffered from severe headache, with much mental 
depression, nausea, backache, and darting pains down the legs. 

Physical Examination. — Emaciated; skin of a peculiar grayish 
yellow hue; tongue thickly coated and flabby; expression listless 
and depressed; heart and lungs normal; pulse rapid, full and 
strong; spleen enlarged and tender, reaching about 6 centimeters 
below border of ribs; liver slightly enlarged; bowels constipated. 

Examination of the Blood. — The blood was examined daily, at 
regular intervals, and showed very numerous quotidian estivo - 
autumnal malarial parasites. Eing-forms and pigmented forms 
were common, and on one occasion two segmenting forms were 
observed. The organisms were most numerous during the latter 
part of the paroxysms. The ring forms were very minute, 
indistinct in outline, and actively amoeboid at intervals. The 
pigmented forms were circular or oval in shape, and contained 



126 ESTIVO- AUTUMNAL MALARIA 

one or two nearly black pigment dots. The pigment was im- 
motile and the organisms showed no amoeboid motion. The 
segmenting forms were both intracorpuseular, and in one in- 
stance the number of segments was six; in the other, eight. 
In one instance a peculiar double ring-form of the parasite was 
observed, which suggested a process of division. Numerous 
corpuscles were observed to contain two ring-forms. 
Treatment. — Quinine .65 every four hours. 

The temperature chart in this ease shows an unusually high 
range of temperature for the quotidian estivo- autumnal infection, 
but is not otherwise remarkable. It resembles, even more than 
that of Case No. 1, an ordinary double tertian chart, and it 
would obviously be impossible to make a diagnosis of estivo - 
autumnal infection from the chart, without the aid of the 
microscope. The chart, is, however, a beautiful example of the 
temperature curve in the quotidian estivo -autumnal infections, 
as contrasted with the totally different temperature curve of the 
tertian type of the infection. It also shows how little a chart 
can be depended upon in making a diagnosis of the type of 
malaria present in a given case. It is safe to say that upon 
simple inspection, this, or, in fact, almost any quotidian estivo - 
autumnal chart, would be considered as a chart of double tertian 
malaria, and very justly so. The microscopical examination of 
the blood is the only means by which the diagnosis can be 
cleared up in such cases as these, and it should never be 
neglected, as it is of infinite importance to the patient whether 
or no he is suffering from the benign double tertian or the too 
often malignant estivo-autumnal infection. The prompt subsi- 
dence of so pronounced an infection, under large, repeated doses 
of quinine, is also worthy of attention. 

Case III: Chart 8 — Cecil Taylor. — The history in this case 
is briefly as follows: The patient had never been in Cuba, and 
apparently his malaria was contracted at Fortress Monroe, as he 
gave no history of previous attacks. His illness began with a 
slight chill, nausea, vomiting, and severe headache and back- 
ache. He also had some abdominal tenderness and a slight epis- 
taxis. His temperature reached 103.8° F. after the chill. 

Physical examination showed an enlarged spleen, general 
abdominal tenderness, dry, hot skin, flushed face, injected con- 



CHABT FAIRLY TYPICAL 129 

junctivaa, and a pointed, tremulous tongue thickly covered with a 
white fur; the pulse full and rather slow. The case was regarded 
at first as one of typhoid fever, but no Widal reaction could be 
obtained, and examination of the blood showed large numbers of 
typical quotidian estivo- autumnal parasites. 

Examination of the Blood. — The blood showed numerous in- 
tracorpuscular "ring-forms" of the estivo -autumnal parasites of 
the quotidian type, and also a few crescents. The intracorpus- 
cular parasites were very small, rather dimly outlined, actively 
amasboid at times, and often corpuscles were seen containing two 
parasites. The infected corpuscles were smaller than normal, 
dark green in color, and often crenated. No pigmented forms 
were observed. 

The crescents were remarkable because of their plump appear- 
ance and small size. They contained perfectly motionless, almost 
black pigment, in the form of short rods; their protoplasm had 
a peculiar refractive, ground -glass appearance, and in every in- 
stance a darker colored, greenish double outline was to be seen 
surrounding them. They were easily seen to be dissimilar from 
the more common tertian estivo -autumnal crescents. 

Treatment. — Quinine, in .40 doses, given everv four hours, 
caused a disappearance of the fever in two days. 

In this case the temperature chart is not as typical as in the 
other cases cited, and is therefore more interesting. During the 
first two days of illness the temperature showed hardly any 
remission, but after that the remissions occurred as usual. It is 
difficult to explain this by any other hypothesis than a double 
infection, two groups of parasites reaching maturity within a few 
hours of each other. This explanation is further strengthened 
by the fact that on the 29th two paroxysms occurred; but this 
time the last paroxysm occurred after the remission of the first. 
As a whole, however, the chart is a fairly typical one of quo- 
tidian estivo -autumnal fever. It will be seen that the patient 
had no distinct chills, but chilly sensations. 

Case IV: Chart 9 — Robert S. — Patient was forty years 
old and had been in the service for thirteen years; Had always 
been well. Had had a slight cough at times during the past two 
years, but physical signs were negative. The sputum showed no 
tubercle bacilli. Was taken sick in Tampa, Florida, in 1898. 



130 ESTIVO- AUTUMNAL MALARIA 

Had chills daily for three or four days. Recovered from this 
attack and went with his regiment to Santiago. He remained 
there until January, 1899, having several attacks of malarial 
fever and being unfit for duty about six weeks in all. Arrived 
at the hospital January 23, 1899. While here had a quotidian 
temperature and chilly sensations, with rarely a distinct chill. 
Suffered from headache, loss of appetite, pain in back and limbs, 
and slight nausea. Had no distinct sweats. 

Physical Examination. — Patient somewhat emaciated and very 
anemic ; skin bronzed and rather moist ; tongue flabby and 
coated ; spleen enlarged ; heart and lungs normal ; abdomen 
rather tender; pulse full and rapid. 

Examination of the Blood. — The blood contained large numbers 
of ring -forms of the quotidian estivo- autumnal parasite and a 
few crescents. In several examinations only two pigmented para- 
sites were seen. 

The intracorpuscular rings were similar in appearance to 
those already described, being minute in size, rather dim in out- 
line, and always perfectly round. The pigmented forms were 
circular in shape, more sharply outlined than the "rings," and 
the pigment consisted of one black dot situated in the center of 
the parasite. The pigment was perfectly motionless, and the 
parasites were not amoeboid. The infected corpuscles were very 
dark green in color. 

The crescents observed were small and very plump, and showed 
a double outline. An intracorpuscular crescent was observed 
during our examination. 

Treatment. — Quinine, .40 doses every four hours reduced the 
temperature to normal very promptly. 

The temperature curve in this case is remarkable for its regu- 
larity, and because of its resemblance to the temperature curve 
seen in pulmonary tuberculosis. This resemblance, together with 
an acute bronchitis present, caused the case to be considered as 
one of phthisis until the microscope cleared up the diagnosis, and 
quinine wrought a cure. The quotidian paroxysms, it will be 
noted, occurred with great regularity, and the temperature went 
below normal after each paroxysm. Without a blood examination 
it would be impossible, from the chart, to differentiate the two 
diseases, and it is in such cases as these that the value of a 
microscopical examination is shown. No distinct chills were 



QUOTIDIAN TYPE 131 

noted at any time, the patient complaining only of chilly sen- 
sations. 

Case V: Chart 10 — Charles S. — The patient went with his 
regiment to Santiago in August, 1898. Was there about three 
weeks, when he was taken suddenly ill with "fainting spells," 
as he expressed it. Was taken to the hospital and suffered from 
severe headache, slight chills and nausea and night sweats. Was 
in the hospital about two weeks. He then returned to duty, but 
had several relapses, the last one occurring about five weeks be- 
fore arrival at this hospital, on December 11, 1898. Since being 
at this hospital, he has had two attacks, attended with chilly 
sensations, nausea and severe headache. 

Physical Examination. — Patient somewhat emaciated and very 
anemic; skin yellow; tongue flabby and coated; heart and lungs 
normal; spleen not appreciably enlarged; liver enlarged; abdo- 
men distended, but not tender; bowels constipated. 

Examination of the Blood. — The blood contained a few typical 
ring-forms of the quotidian estivo- autumnal parasite, the "rings" 
being small, circular in shape, dimly outlined, actively amoeboid 
at times, and unpigmented. Pigmented forms were also numer- 
ous. These were more sharply denned than the "ring -forms," 
were less than one -fourth the size of the infected corpuscle, and 
the pigment occurred as a single dot, situated at the center or at 
one side of the parasite. The pigment was perfectly motionless 
and almost black in color. No amoeboid motion was noted in 
the pigmented forms. The infected corpuscles were always 
shrunken and crenated. 

Treatment. — Quinine, in .40 doses every four hours, reduced 
the temperature to normal in two days. 

The temperature chart in this case is that of a typical 
quotidian estivo -autumnal infection, the paroxysms occurring 
regularly, and the chart resembling that of a double tertian 
infection. 

From the study of a large number of cases of this type of 
malaria, of which the five cases given are fair examples, the 
conclusion is inevitable that there occurs a type of malarial fever, 
due to an estivo -autumnal parasite, and characterized by quotidian 
paroxysms. These paroxysms are due to the ripening of a single 
generation of a peculiar and characteristic form of the estivo- 



132 ESTIVO- AUTUMNAL MALARIA 

autumnal parasite, which completes its cycle of development in 
the blood in approximately twenty -four hours. 

In blood secured by puncture of the spleen, all stages of the 
development of this organism can be studied, and each stage 
differs markedly from the estivo- autumnal parasite causing par- 
oxysms every forty -eight hours. 

The points to be noted in the differentiation of the quotidian 
estivo -autumnal parasite are: 

1. During its hyalin stage its minute size (about one- sixth 
of the corpuscle) ; its perfectly circular ring -shape; its very active 
amoeboid motion, which occurs at intervals, and is so rapid that 
it must be carefully watched for ; its indistinct outline at the 
earliest stage; the very dark green color of the infected corpuscle 
and its wrinkled or crenated appearance, and the fact that often 
more than one parasite occurs in a corpuscle. 

2. During its pigmented stage its small size (about one -fourth 
of the corpuscle); its circular shape and loss of "ring-form" 
before pigmentation; its very sharply defined outline; its pig- 
ment, consisting of one or two coarse granules, perfectly motion- 
less; its multiple occurrence in corpuscles, and their very dark 
green crenated appearance. 

3. During segmentation, which takes place within the red 
corpuscles, and the number of segments is six or eight. 

4. During phase of crescents which are small and plump, 
contain a small amount of pigment, and always show double 
outline. 

5. The cycle of development, lasting twenty -four hours. 
There is no difficulty in securing typical temperature charts 

of this form of malarial fever if quinine be withheld; but if it 
be given in small doses, or at long or unsuitable intervals, the 
regularity of the temperature curve is lost and, from a consid- 
eration of the chart, it becomes impossible to tell with what 
form of malaria we are dealing. To this is undoubtedly due 
the fact that this form of malaria has not been more generally 
recognized. 

CASES OF TERTIAN ESTIVO-AUTUMNAL FEVEK 

In the chapters which have preceded this I have called atten- 
tion to the fact that the majority of cases of estivo -autumnal 
fever present paroxysms occurring, approximately, every forty- 



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CARE IN TREATMENT 135 

eight hours. These tertian paroxysms are peculiar in that while 
they occur every other day, each paroxysm is prolonged so that 
it lasts considerably over twenty -four hours, and often almost 
forty -eight hours. This type of malarial fever is further char- 
acterized by a peculiar temperature curve, which was first 
described by Marchiafava and Bignami. The analysis of the 
temperature curve in these cases shows the following charac- 
teristics: a rapid and sudden rise, a stage with slight remis- 
sions, a pseudocrisis, a precritical rise, during which the 
temperature reaches a higher point than it had previously, and, 
lastly, the true crisis, in which the temperature rapidly falls. 

This peculiar temperature curve is presented in all uncompli- 
cated cases of tertian estivo-autumnal fever, where quinine has 
not been administered. In cases which are infected by two 
groups of the parasites ripening at different periods, or by the 
tertian or quartan parasites, or, again, by both the quotidian 
and tertian estivo-autumnal parasites, this peculiar temperature 
curve will not be exhibited, nor will it be in cases which have 
received small doses of quinine or quinine at long intervals. 

In order, then, to secure a typical temperature chart of the 
tertian estivo-autumnal fever, we must have a patient infected 
by a single group of parasites, and must withhold all quinine 
for several days. It is safe to say that all the confusion exist- 
ing to-day regarding the types of estivo-autumnal fever is due 
to one of two factors, infection by more than one variety of 
malarial parasite, and the improper and untimely administration 
of quinine. The first factor can only be eliminated by the use 
of the microscope in diagnosis, and the second only by an 
earnest scientific spirit on the part of the physician, so strong 
that he will be willing to withhold quinine long enough to 
secure a proper knowledge of the character of the case which he 
is called upon to treat. Medicine, to-day, has reached a stage 
where the so-called diagnostic terms of "remittent" and "inter- 
mittent" malarial fevers are of little exact meaning; and earnest 
effort should be made to substitute for them, in medical nomen- 
clature, the more scientific terms, tertian, quartan, and quo- 
tidian and tertian estivo-autumnal malarial fevers. 

The following cases are selected from a large number because 
they are typical of the tertian estivo-autumnal fever, and because 
they presented all forms of the tertian estivo-autumnal parasite, 
for this form of malarial fever is dependent upon a character- 



136 ESTIVO- AUTUMNAL MALARIA 

istic parasite, possessing well -recognized differences from the 
parasite causing the quotidian form of the fever, and which is 
easily differentiated by the microscope, when one has become 
accustomed to the appearances presented by it in the blood. 

From the following cases, in which I have especially con- 
sidered the character of the temperature curve and the parasites 
present, I hope to prove conclusively the occurrence and dis- 
tinct character of the tertian form of estivo- autumnal fever: 

Case I: Chaet 11 — Sidney C— Age, 23. The patient arrived 
at Santiago, Cuba, in August, 1898. On September 20, 1898, 
he was taken sick with a chill, which was followed by a high 
temperature. He had chills every other day for several days, and 
suffered from nausea and vomiting, severe headache and legache, 
and drenching perspiration. He had several attacks during the 
next two months and was finally sent to the Simpson hospital, 
where he arrived on December 11, 1898. On December 17 
he had a rise of temperature, accompanied by chilly feelings. 
This paroxysm was succeeded by three others, all accompanied 
by severe headache and backache, nausea, and great nervous 
prostration. 

Physical Examination. — Patient somewhat emaciated; skin 
yellowish; mucous membranes pale; cheeks flushed; eyes bright; 
tongue broad and coated ; heart and lungs normal ; abdomen 
rather tender; bowels constipated. Marked mental depression 
and general debility. 

Examination of the Blood. — The blood was examined at fre- 
quent intervals, and numerous ring-forms, pigmented rings, and 
larger pigmented forms of the tertian estivo -autumnal parasite 
were found. No segmenting forms were observed. The "ring- 
forms" were larger than those of the quotidian parasites, being 
about one -fourth the size of the infected corpuscle, irregular in 
shape, most of them presenting an enlargement at some portion 
of their periphery, thus causing the so-called "signet-ring" ap- 
pearance. They were very refractive and sharply outlined, look- 
ing as though they were cut or stamped into the corpuscle; the 
protoplasm was clear and the amoeboid movements were sluggish. 
The "ring-form" was sometimes lost, a clear, circular hyalin 
disk resulting. No corpuscles were observed to be infected by 
more than one parasite, and the corpuscle itself, although more 
greenish in color than the uninfected ones, was very much less 



THE TEMPERATURE CURVE 137 

altered in appearance than in the quotidian infection, and but 
seldom crenated. 

The pigmented rings and pigmented bodies were present in 
small numbers. The pigmented rings showed a few fine pig- 
mented granules, generally in the dilated portion of the ring, 
and these granules were often in rapid motion. These pig- 
mented rings still showed amoeboid motion, sometimes very 
noticeable. 

The pigmented parasites were larger than the rings, being 
nearly one -half as large as the infected corpuscle; they were 
very sharply defined, the protoplasm being very refractive and 
finely granular in appearance. The pigment was in the form of 
fine reddish brown granules, and had a marked vibratory motion. 
The amoeboid motion of these parasites was very sluggish, and 
in some had entirely disappeared. 

Treatment. — Quinine, .40 every four hours, reduced the tem- 
perature in two days, and its continued use resulted in recovery. 

A consideration of the temperature chart in this case shows 
a beautiful illustration of the peculiar temperature curve in this 
type of malarial fever. Quinine was withheld until the occur- 
rence of the fourth paroxysm. It will be seen that the par- 
oxysms occurred at intervals of forty-eight hours approximately, 
and that they lasted from thirty -six to forty -eight hours. 
It also shows well the several characteristics of the curve noted 
before. Taking the paroxysm of the 21st for example, we see 
beautifully illustrated the rise, the period of slight remissions, 
the pseudocrisis, the precritical rise, in which the temperature 
reached the highest point, and, lastly, the crisis, in which the 
temperature gradually returned to normal. The intervals be- 
tween the paroxysms were short, as shown by the chart. It will 
also be noted that two of the paroxysms were accompanied only 
by chilly feelings, while two commenced with distinct chills. As 
a general rule the temperature goes to normal or below, during 
the intervals, but in this case it did not. 

Case II: Chart 12 — Paul R. H. — Age, 21. Patient ar- 
rived in Cuba on December 17, 1898. Was taken sick March 
13, 1899, with severe pain in the head, chill, high fever, and 
nausea, and vomiting. Was supposed to be suffering from 
typhoid fever, but felt better after a week in the hospital and 



138 ESTIVO- AUTUMNAL MALARIA 

was up and about. Ou April 6, the day before he boarded 
the steamer on his way to Fortress Monroe, the fever returned, 
accompanied by the same symptoms. Arrived at the Simpson 
hospital on April 12. Since arrival he has had four chills, oc- 
curring every other day, but not very severe, accompanied by 
nausea, vomiting, headache, high temperature, and pain in the 
back and legs. 

Physical Examination. — Patient looked very ill. Greatly ema- 
ciated, skin yellow, cheeks flushed, eyes bright, tongue broad 
and coated with yellowish fur. Heart and lungs normal. Pulse 
rather weak. Spleen slightly enlarged. Liver normal. Abdo- 
men rather tender. Bowels constipated. 

Examination of the Blood. — The blood was examined at fre- 
quent intervals and always showed numerous ring -forms and 
pigmented rings of the tertian estivo- autumnal parasite, similar 
in every respect to those described in Case I. No segmenting 
forms or crescents were found in the peripheral circulation. The 
parasites were most numerous just before the paroxysms. 

Treatment. — Quinine, .50 every six hours. Recovery. 

The temperature chart in this case is a typical one of the 
tertian estivo -autumnal fever. It will be seen that there were 
four paroxysms in all, and that each of them showed the char- 
acteristic temperature curve, although the paroxysm of the 23d 
is slightly atypical, in that after the pseudocrisis there occurred 
a slight remission before the final rise and the crisis. That of 
the 27th is very typical. In no other malarial disease will a tem- 
perature chart like this be seen, and it is actually diagnostic of 
the type of infection present. 

Case III: Chart 13— A. H. Hall. — The patient, while in 
Santiago, suffered from malarial fever, having chills nearly every 
other day, accompanied by high fever, severe headache, backache, 
and nausea. Arrived at Fortress Monroe on January 23, 1899. 
Has had several paroxysms of fever, accompanied by chilly feel- 
ings, but no distinct chill, severe headache, and backache, some 
nausea, and general muscular pain. 

Physical Examination. — The patient showed but little emacia- 
tion and appeared physically well. There was some anemia, the 
tongue was coated, the bowels constipated. Heart, lungs, and 
liver apparently normal. The spleen was enlarged, reaching half 



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TERTIAN MALARIA 141 

way to the umbilicus. There was much meutal depression pres- 
ent. Pulse full and regular. 

Examination of the Blood. — The blood was examined fre- 
quently and numerous pigmented and unpigmented tertian estivo- 
autumnal parasites were found, most numerous just before or 
some time after a paroxysm. 

Treatment. — Quinine, .40 every four hours. Recovery. 

In this case the temperature chart is again typical of the 
tertian estivo- autumnal infection, and would easily be recog- 
nized on simple inspection. The occurrence of the paroxysm on 
every third day, the length of the individual paroxysm, the pe- 
culiar curve exhibited, all prove conclusively the type of malarial 
disease present, even without the aid afforded by the microscope 
in detecting the characteristic parasite. 

Case IV: Chart 14 — Sullivan. — The patient arrived at 
Santiago in August, 1898. Was there about two weeks when 
he was taken suddenly ill, having a chill, high fever, nausea 
and vomiting, and great mental depression. Chills recurred 
every third day, and were always accompanied by intense head- 
ache and fever. Arrived at Simpson hospital on December 11, 
1899, and on the 16th had chilly sensations and a rise of tem- 
perature. He had two paroxysms after this, accompanied by 
fever, intense headache, nausea, general muscular pain, and 
mental depression. 

Physical Examination. — Patient appears well, save for some 
anemia and listlessness. Skin is slightly yellow, tongue slightly 
coated. Heart, lungs, and liver apparently normal. Spleen not 
appreciably enlarged. Bowels constipated. Pulse full and regular. 

Examination of the Blood. — Numerous examinations of the 
blood were made, and pigmented and unpigmented ring-forms 
of the tertian estivo- autumnal parasites were found as well as 
large pigmented forms. Several segmenting forms were observed. 

The pigmented and unpigmented ring -forms have already 
been described under Case I. The large pigmented parasites 
were nearly half as large as the infected corpuscle, and con- 
tained numerous fine granules of pigment, generally collected 
near the center of the organism. The parasites were very 
sharply cut and refractive. In some of the pigmented forms 
the pigment was collected in a solid block at the center, and 



142 ESTIVO- AUTUMNAL MALARIA 

faint radial striations could be made out dividing the organism 
into several segments. 

The segmenting forms observed were extracorpuscular, and 
consisted of blocks of pigment with ten or more oval segments 
arranged around them. The segments were very minute. 

Treatment. — Quinine .40 every four hours. Recovery. 

The temperature chart in this case is interesting in that each 
of the three paroxysms presents a modification of the typical 
tertian estivo- autumnal curve. In the first paroxysm there is 
no stage of slight remissions, there being a rapid initial rise 
and almost immediately a pseudocrisis, in which the temper- 
ature reached normal. This was immediately succeeded by the 
precritical rise and followed by the crisis. 

In the second paroxysm there is also no stage of slight 
remissions, but the pseudocrisis is more normal and the pre- 
critical rise more gradual. 

The third paroxysm is marked by a well-defined stage of 
slight remissions, but the pseudo-crisis is almost absent. 

Such slight modifications as these are very common in ter- 
tian estivo -autumnal cases, but they do not in the least affect 
the general character of the temperature curve, nor cause a 
moment's doubt as to the nature of a case showing such a 
temperature curve as is here presented. Such temperature curves 
are uniquely characteristic of, and are only associated with, the 
tertian estivo -autumnal infections. 

Case V: Chart No. 15— Charles Connor. — Age, 25. 
Arrived at Santiago, Cuba, in August, 1898. Was there about 
one month, when he had a sharp chill followed by high temper- 
ature. Chills occurred for a while on every third day, but later 
became irregular. They were always followed by a high temper- 
ature. He was admitted to the hospital there five different 
times, each apparent recovery from the fever being followed by 
a relapse as soon as he returned to duty. During the paroxysms 
he suffered from very severe headache, muscular pain, nausea, 
and vomiting. He arrived at the Simpson hospital on December 
11, 1898. Had chilly sensations and headache on the 15th, fol- 
lowed by a rise of temperature. He had three slight paroxysms 
afterward, accompanied by slight chilly sensations. 

Physical Examination. — Patient emaciated and anemic, Skin 











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TERTIAN ESTIVO - AUTUMNAL INFECTION 145 

yellow, tongue flabby and coated. Heart and lungs normal. 
Spleen greatly enlarged, reaching nearly to the umbilicus. Liver 
dullness normal. Bowels constipated. Abdomen tender. 

Examination of the Blood. — The blood in this case showed 
numerous pigmented ring-forms of the tertian estivo- autumnal 
parasite and also numerous crescents. The ring -forms have 
already been described under Case I. 

The crescents were very much more slender and larger than 
those of the quotidian estivo -autumnal parasites, and contained 
much more pigment of a more reddish color. The double out- 
line was much less common, but the tertian crescents were more 
refractive. 

In this case the temperature chart is not as typical as the 
preceding ones, but it is typical of the more chronic form of 
the tertian estivo -autumnal infection. The paroxysms occur every 
forty -eight hours approximately, but it will be noted that the 
range of temperature is not as high and that there seems to be 
a tendency toward a spontaneous decline of the infection. The 
chart is curious in that there seems to be a reversal of the ordi- 
nary temperature curve, the highest temperature being reached 
during the initial rise; but even in this chart the temperature 
curve is, on the whole, so characteristic that a diagnosis of 
tertian estivo -autumnal fever could easily be made from an 
inspection of it. 

From the cases of quotidian and tertian estivo -autumnal ma- 
larial fever considered it will be seen that no differentiation is 
possible from a consideration of the clinical symptoms, save that 
in the first -named the chill or chilly sensations occur every day, 
while in the latter they occur every other day. A consideration 
of the temperature charts, however, shows such a marked differ- 
ence in the temperature curve that we must admit that we are 
dealing with two distinct types of infection. The quotidian 
estivo -autumnal type shows a simple intermittent temperature 
curve, indistinguishable from a double tertian, while the tertian 
estivo -autumnal type presents a most peculiar and characteristic 
temperature curve, entirely different from that shown in any 
other type of malarial fever, and diagnostic in itself. When to 
this is added the fact that the tertian form is due to a distinct 
and easily differentiated parasite, as I have shown, the conclusion 
is inevitable that there are two varieties of estivo -autumnal fever, 



146 ESTIVO- AUTUMNAL MALARIA 

the quotidian and tertian, and that each is due to a characteristic 
parasite, as first shown by Marchiafava and Bignami. 

The tertian estivo- autumnal parasite differs from the quotidian 
parasite in the following particulars: 

1. During the hyalin stage the rings are large, being from 
one-third to one-fourth the size of the infected corpuscle; the 
signet -ring shape; the sluggish amoeboid motion; the clear-cut 
and refractive outline, which is not so distinctive after the quo- 
tidian parasite has developed for some hours; the less wrinkled 
and lighter green infected corpuscle; the occurrence of only one 
parasite in the infected corpuscle. 

2. During the pigmented stage, larger size, one -half of the 
corpuscle; the pigmented ring-forms; the continuance of amoe- 
boid motion; more sharply defined and refractive; the granular 
protoplasm; the finely granular pigment, which is motile; the 
occurrence of only one parasite in a corpuscle, and the lighter - 
colored, seldom -crenated infected corpuscle. 

3. During the segmenting stage, the occurrence of segmen- 
tation outside the corpuscle; the number of segments, ten to 
fifteen. 

4. The larger, more narrow, more deeply pigmented crescents. 

5. The cycle of development — forty -eight hours. 

These morphological differences considered together with the 
totally different temperature charts should be sufficient to dis- 
tinguish the tertian from the quotidian type of estivo - autumnal 
malaria, aud I am satisfied that careful study will confirm in every 
detail the truth of the existence of the two types of fever de- 
scribed. 



CHAPTER XIV 

THE PERNICIOUS FORMS OF THE ESTIVO- AUTUMNAL MALARIAL 
FEVERS 

In this chapter I shall describe the pernicious forms which 
the estivo- autumnal malarial fevers sometimes assume. It should 
be distinctly understood that there is no parasite which pro- 
duces only pernicious malarial fever, but that the same parasite 
which causes the mildest estivo -autumnal infection is also capable 
of causing the most rapidly fatal form. As the vast majority of 
fatal cases of malarial fever are due to the estivo -autumnal 
parasites, it is at once easily seen how important it is to be 
able to differentiate them. Any malarial fever may suddenly 
develop malignancy and cause the death of the person infected; 
hence the absurdity of trying, as some authors have, to classify 
such cases as disease entities, dependent upon a peculiar and 
special parasite. 

The great majority of pernicious attacks of malaria, in the 
northern altitudes, occur in the summer and autumn, and are 
rare, while in the tropics they occur throughout the year and 
are common. Most pernicious attacks of estivo -autumnal fever 
occur in patients who have previously suffered from severe 
paroxysms, which have not been properly treated, and the per- 
nicious symptoms often develop during such a paroxysm. 

Why do certain cases develop pernicious characteristics? Bas- 
tianelli and Bignami have carefully studied the development of 
such cases and have come to the following conclusions: 

"The conditions through which a malarial fever becomes 
pernicious are : 

"I. That the infection be produced by one of the varieties 
of the estivo -autumnal parasite. [This condition will not hold, 
as several authorities have observed pernicious cases due to the 
tertian parasite.] 

"II. The second condition relates to the abundance of the 
parasites, and it may be stated as follows: In pernicious fevers, 
if one take into consideration not only the examination of blood 

(147) 



148 ESTIVO- AUTUMNAL MALARIA 

from the finger, but also the condition in the vessels of the vari- 
ous organs, it is a striking point that, however the distribution 
of the parasites may vary in individual cases their total number 
is always considerable. As regards the distribution, one may 
make the following distinctions. There exist: 

"1. Cases in which the number of parasites is most abundant, 
yes, enormous, in the brain, while all the organs are less uniformly 
invaded. These are the commonest forms of pernicious fever, 
and are usually accompanied by coma. 

"There are some cases in this category in which the number 
of parasites in the blood of the finger, of the spleen, of the 
bone-marrow, etc., is enormous, while the number in the brain 
is scanty. Clinically, the absence of cerebral phenomena is noted. 

"2. Cases in which the number of organisms is absolutely 
and relatively scanty in the bone -marrow, in the spleen, and in 
the liver, while they may be relatively few in the blood of the 
finger, and yet other organs are crowded with the parasites. 
Among these the following localizations are to be made out: 

"a. The brain and the meninges are filled with parasites, 
either in sporulation or in all their stages of development. Clin- 
ically, there are cerebral phenomena. 

"&. The stomach and intestines are chiefly invaded. In these 
organs the mature forms of the parasite are usually found; these 
are the cases of pernicious fever which present clinically intestinal 
phenomena." 

Besides the reasons above given, it is probable that the 
amount of toxins secreted by the parasites have much to do with 
the production of pernicious symptoms, as well as the physical 
condition of the infected individual and his surroundings as 
regards climate, food, hardships, etc. 

The pernicious forms of estivo- autumnal fever are classified 
in two ways, i. e., from the character of the temperature curve, 
and from the most prominent symptoms present. 

Under the first classification we may have tertian, quotidian, 
remittent, or larval pernicious fever. 

Under the second classification we may have comatose, de- 
lirious, tetanic, eclamptic, hemiplegic, bulbar, ataxic, dysenteric, 
choleraic, algid, cardialgic, diaphoretic, hemorrhagic, pneumonic, 
and the bilious pernicious fevers. 

Pernicious attacks are sometimes very rapidly fatal, while at 
others they are more gradual in their course. As a rule, the per- 



DESCRIPTION OF COMMON FORMS 149 

nieious symptoms develop gradually, but sometimes very ab- 
ruptly. The coma may strike the patient like a lightning-flash, 
death following shortly, or it may persist for several days. 

DESCRIPTION OF THE MOKE COMMON FORMS OF THE PERNI- 
CIOUS ESTIVO- AUTUMNAL MALARIAL FEVERS 

The Comatose Form. — (Apoplectic form.) This is the most 
common form of pernicious malarial fever and occurs in two 
ways: either as a sudden attack or as a gradually developing 
comatose condition during an attack of the fever. 

The sudden development of coma is rare, and, unless at once 
recognized and properly treated, almost invariably fatal. In this 
form the patient, who has not felt unwell enough to cease his 
occupation, is suddenly stricken with a profound coma, falls to 
the ground and, in the fatal cases, does not again regain con- 
sciousness. The face is suffused, the pupils contracted, the respi- 
rations hurried and labored, the pulse at first full and bounding, 
later soft, rapid, and thready. Such attacks, if untreated, seldom 
last over two days. This form of pernicious malaria is very often 
taken for apoplexy, and the microscopical examination of the 
blood is the only method to be relied upon in making a diag- 
nosis, as the temperature is irregular, seldom reaching 103° F., 
and often subnormal. 

The Typical Comatose Form. — In this, the most common form 
of pernicious malaria, the coma develops more or less gradually 
during an attack of the fever. The attack begins usually with 
a slight chilly sensation, languor, nausea, or vomiting, severe 
headache, and a rise of temperature. In some cases a marked 
nervous condition is present, and even delirium may precede the 
coma. As a rule the patient is restless and mentally depressed. 
Following this there develops a tendency to somnolence, which 
deepens into stupor and finally eoma. The unconsciousness is 
complete and the patient lies either perfectly quiet or there are 
restless movements of the arms and legs. The skin often as- 
sumes an icteric hue and is hot and dry; the pupils are generally 
equally contracted, but may be unequally or equally dilated. The 
icteric hue may be very noticeable in the conjunctivae, this symp- 
tom, in infected regions, often leading to a diagnosis of yellow 
fever. The face, when the malarial infection is of recent origin, 
is flushed and may be cyanotic; in old infections the face may 



150 E8TIVO- AUTUMNAL MALARIA 

be pale; slight spasms of the muscles of the face are not infre- 
quent. The tongue is tremulous, dry, and thickly coated. The 
occurrence of slight hemorrhages into the skin is sometimes ob- 
served. There may be hemiplegia present, or even total paralysis. 
The patellar reflex may be absent or slightly increased. The 
respirations may be slow and quiet, interrupted, or rapid and 
stertorous. The Cheyne- Stokes type of respiration is sometimes 
observed. The pulse is generally slow and full and incompres- 
sible at first, but becomes rapid and weak as the paroxysm pro- 
gresses. As a rule the faeces and urine are passed involuntarily, 
but in some cases retention of urine occurs. 

The duration of the coma is variable, lasting from a few 
hours to three or four days. As a rule it does not persist longer 
than twenty -four or thirty -six hours. 

In cases having a fatal termination the pulse becomes thready, 
rapid, and intermittent ; the respiration irregular, labored, or 
shallow; the skin pale and bedewed with cold perspiration, and 
death occurs. In cases which recover the temperature falls, 
accompanied by perspiration, the consciousness is slowly re- 
gained, preceded usually by a quiet sleep. 

In many cases this improvement is only apparent, and the 
patient relapses, in a few hours, into a second paroxysm, 
and from this, even into a third, which usually results fa- 
tally. Between the paroxysms the mental condition is one 
of torpor or great mental depression, accompanied by severe 
cephalgia. 

Sometimes following the coma a condition of active delirium 
develops which may endanger the patient's life. 

As regards the temperature in this form of pernicious ma- 
larial fever, it may be said that it is irregular. Some cases 
present a high temperature throughout, between 103° and 
105° F., while in others the temperature remains mostly normal, 
or below that. In fatal cases the fever, if present, declines 
some hours before death; in other cases it ascends, and Manson 
cites temperatures of 110° and 112° F. in such cases. As an 
illustration of how low the temperature may run, the following 
temperature record of a fatal case of quotidian estivo- autumnal 
fever may prove interesting. This case was observed by the 
author, and the morning and evening temperatures only are 
given, as there was no rise during the intervening hours. The 
temperature record is as follows: 



OTHER CEREBRAL PERNICIOUS FORMS 151 



July 15, A. M., 


98.4° F. 


; P. M., 101.° F. 


July 16, A. M., 


99° F. | 


; P. M., 99.6° F. 


July 17, A. M., 


98° P. : 


; P. M., 97.8° F. 



July 18, A. M., 96.4° F.; p. M., 98.° F. 
July 19, A. M., 100.2° F.; p. M., 98.° F. 
July 20, a. m., 103.° F. ; p. m., Died. 

In this case the disease was not recognized by the attending 
physician until the 19th of July, when the blood was examined 
by the author and found to contain large numbers of quotidian 
estivo- autumnal parasites. 

Auscultation of the lungs in the comatose form of pernicious 
malarial fever often demonstrates the presence of rales both at 
the apices and the base of the organs, and, not rarely, marked 
signs of extensive congestion. The right heart is generally, 
upon percussion, found dilated, and a systolic murmur is some- 
times heard at the mitral valve. 

One attack of comatose pernicious fever is apt, if untreated, 
to be followed by another, and this by another, and any of 
these attacks may prove fatal. The disease may prove fatal 
even after quinine has been properly administered, and even 
though it has been administered during a preceding comatose 
paroxysm. 

The number of parasites found in the peripheral blood is not 
always a criterion as to the perniciousness, as one of the most 
rapidly fatal cases I have ever observed showed but few parasites 
in the peripheral blood. The capillaries of the brain in this 
case, however, showed multitudes of the parasites. 

The symptoms in the comatose form of pernicious estivo - 
autumnal malarial fever are probably as much due to poisonous 
materials elaborated by the parasites as by their special local- 
ization in the cerebrum. 

OTHEE CEEEBEAL PEENICIOUS FOEMS OF ESTIVO -AUTUMNAL 
MALAEIAL FEVEES 

Besides the comatose form of pernicious malaria are several 
other forms in which the cerebral symptoms predominate. 
Among them may be mentioned the delirous form, in which 
the patient has hallucinations, followed by violent excitement; 
the tetanic form, characterized by trismus, convulsions, opisthot- 
onos, and delirium ; the eclamptic form, especially common in 



152 ESTIVO- AUTUMNAL MALARIA 

children, which is very similar in symptomatology to cerebro- 
spinal meningitis, there being vomiting, fever, headache, pain 
in the back of the neck, with stiffness, convulsions, and coma ; 
the Jiemiplegic form, characterized by hemiplegia, associated with 
coma; the amaurotic form, in which the comatose symptoms are 
followed by complete blindness, which may be very persistent. 
Blindness may also occur during the attack. 

The attacks associated with symptoms of bulbar paralysis are 
very interesting, and have been studied by Marchiafava, Bignami, 
and Bastianelli, chiefly. Marchiafava thus graphically describes 
the symptomatology of this form of the disease: "The chief 
symptoms are difficulty in articulation, which may even reach 
anarthria, a weak and nasal voice, inferior facial paralysis often 
of one side only, a half-open mouth from which drops the saliva, 
a pendent lower lip, a dry and only slightly movable tongue, 
difficult or abolished deglutition. With these symptoms there are 
sometimes associated disturbances of equilibrium which recall the 
staggering gait of cerebellar disease. In a case of relapse Basti- 
anelli and Bignami noticed an unsteadiness of gait as in drunk- 
enness, diminution of strength of the left side, right facial 
paralysis, deviation of the tongue to the left, difficulty in speak- 
ing, nasal voice, grave prostration, and apathy." 

The symptoms in these cases, under proper treatment, do not 
persist for a longer period than two weeks, as a general rule. The 
ataxic form of pernicious malaria has been carefully studied by 
Angelini and Torti, but it is very rare. 

The Algid Form. — In certain localities the form of pernicious 
estivo- autumnal fever about to be described is not uncommon. 
In some of our southern and middle states the algid form is to 
be observed and is described under a variety of local names. The 
algid symptoms may develop after one or more paroxysms or they 
may be the primary symptoms. 

The characteristic condition is one of collapse, generally very 
great, attended by profuse perspiration, the temperature at the 
same time being more or less elevated ; in some cases the tem- 
perature is subnormal. 

The face of the patient is characteristic, being drawn and 
pinched, the eyes sunken and often the typical Hippocratic facies 
is seen. The skin of the entire body is cold and cyanotic in color, 
and bathed with a cold sweat ; the lips and finger-nails are 
intensely cyanotic ; the tongue is very tremulous, and generally dry 



THE CHOLERAIC FORM 153 

and coated with a peculiar dirty white fur; the pulse is rapid, 
thready, and easily compressible, and generally more or less inter- 
mittent; the heart -sounds are muffled and the second sound 
sometimes inaudible; very often the pulse is imperceptible; the 
respirations are labored and irregular, being rather superficial in 
character, gradually becoming weaker and weaker as death 
approaches; the muscular weakness is extreme, the slightest move- 
ment being often impossible without great effort; the mental 
condition of the patient is one of apathy to his surroundings and 
indifference as to the gravity of his condition; the voice is weak 
and often almost inaudible. The algid symptoms rarely last over 
a few hours and are generally followed by death. No form of 
pernicious malarial fever is less amenable to treatment than is this 
form, and despite the most earnest therapeutic measures, a fatal 
termination is generally the rule, rather than the exception. 
Sternberg, Laveran, Thayer, Marchiafava and Bignami have 
described very typical cases of this form of the disease. I remem- 
ber one very marked case in the person of a volunteer soldier 
who contracted estivo- autumnal fever in Cuba. He had several 
previous paroxysms, none of which showed any great severity, 
but during the last paroxysm algid symptoms developed and 
death occurred after six hours, despite all therapeutic aid. His 
blood showed large numbers of the unpigmented and pigmented 
tertian estivo -autumnal parasites. 

The Choleraic Form. — Certain cases of pernicious estivo- 
autumnal malaria present symptoms very closely simulating those 
of cholera. Marchiafava has studied very accurately a number 
of such cases, and other writers have also observed them. It is 
not rare to have more or less diarrhoea present during estivo- 
autumnal attacks, but in cases presenting the choleraic symptoms, 
the stools suddenly become watery, very profuse, and numerous; 
they may be blood- or bile -stained, and contain mucus in the 
form of small flakes; the profuse diarrhoea leads to collapse, the 
face becoming pinched, the eyes sunken, the skin more or less 
cyanotic; a cold, clammy perspiration covers the skin, the pulse 
and respiration become greatly weakened; the patient, in a husky 
or tremulous voice, complains of severe cramps in the abdomen 
and thighs, and great thirst; he is greatly worried over his con- 
dition, and there is great mental depression. Death is the usual 
result in untreated cases, but where proper therapeutic measures 
are employed, the majority of the cases will recover. The tern- 



154 ESTIVO -AUTUMNAL HALABIA 

perature in the choleraic form is generally elevated. It is rarely 
that a recurrence of the choleraic symptoms takes place, but 
when it does the result is almost invariably fatal. 

This form of pernicious estivo- autumnal malaria simulates 
cholera so closely that the differentiation is very difficult, espe- 
cially in countries where epidemics of cholera are common. The 
microscopical examination of the blood is the only absolutely cor- 
rect method of arriving at a diagnosis in such cases and should 
never be neglected, as the parasites, if the case be malarial, are 
always present in the blood in sufficient number to be found 
with the exercise of a little patience and perseverance. Nowhere 
is the microscope more useful than in the diagnosis of the per- 
nicious forms of estivo -autumnal fever. 

The Cardialgic Form. — This form of pernicious malarial fever 
is comparatively rare, and is generally associated in classifica- 
tion with the gastralgic form. The prominent symptoms are 
severe, agonizing pain in the epigastrium, accompanied by ex- 
hausting vomiting of matter tinged with blood. Hiccough is 
often a very distressing symptom, and severe hematemesis may 
occur. These symptoms occur, as a rule, during the febrile 
stage. 

The patient presents an anxious expression of countenance, 
a dry, glazed tongue, brilliant eyes, the conjunctivas markedly 
congested, a retracted abdomen, cold extremities, hurried respi- 
rations, and a rapid, weak pulse; he suffers intense pain, and 
either groans or calls out under the torture which he is enduring. 
In fatal cases collapse occurs, accompanied by the symptoms 
described under the algid form. 

Laveran, Colin, and Haspel have described cases of the car- 
dialgic and gastralgic form of pernicious estivo -autumnal fever. 
I have seen but one case conforming to this type. The patient 
was a soldier, twenty-two years of age, who had suffered repeat- 
edly from malarial paroxysms in the Philippine Islands. During 
the last paroxysm he had most intense pain over the left nipple 
and the epigastrium, which radiated to the vertebral column and 
down the thigh; the pain was so intense that screams were 
forced from him. He vomited repeatedly blood-stained fluid 
and suffered greatly from hiccough. His temperature reached 
103.4° F., his pulse was very rapid and thready, his extremities 
cold, and he complained of great prostration and was very anx- 
ious regarding his condition. Under repeated hypodermics of 



THE PNEUMONIC TYPE 155 

quinine his condition gradually improved and he eventually 
recovered. 

Tlie Dysenteric Form. — Certain cases of estivo- autumnal fever 
present the characteristic symptoms of dysentery, i.e., frequent 
mucoid and bloody stools, tenesmus, colicky pain in the abdo- 
men, progressive emaciation, fever, etc. I am satisfied that a 
considerable proportion of dysenteric cases occurring in tropical 
countries are due to malarial infection. I am convinced of this 
because of the results of blood -examinations of soldiers returning 
from the tropics. In the routine examination of the blood of all 
cases admitted to the U. S. General Hospital at the Presidio, Cal- 
ifornia, as well as elsewhere, a comparatively large number of 
cases diagnosed as dysentery show malarial parasites in the blood, 
although no marked typical malarial symptoms are present. 
The prompt treatment by quinine resulted almost invariably in 
the disappearance of the dysenteric symptoms and a return to 
health. From my laboratory records I find that 65 per cent 
of the cases of unrecognized malarial fever were diagnosed 
either as chronic diarrhoea or dysentery. This proves how com- 
monly dysenteric symptoms in the tropics are due to malarial 
infection, and how important a microscopical examination of the 
blood is in all cases of dysentery occurring in tropical and sub- 
tropical climates. 

The Diaphoretic Form. — This form of pernicious estivo- 
autumnal fever is characterized by the occurrence of very pro- 
fuse sweating, so severe as to produce collapse and even death. 
This form of the disease is comparatively rare. 

The Hemorrhagic Form. — Marchiafava and Laveran have de- 
scribed cases of pernicious malarial fever characterized by severe 
hemorrhages into the skin and mucous membranes, as well as 
the occurrence of hematomesis, epistaxis and hemoptysis. These 
symptoms may be so severe as to cause collapse and death. The 
temperature is extreme in most of this class of cases. This 
form of the disease is undoubtedly very rare, and I have never ob- 
served such a case. Epistaxis, even of quite severe character, 
is not, however, a very rare symptom in attacks of estivo- autumnal 
malarial fever. I have observed a large number of cases which 
presented epistaxis during the paroxysms of a malarial infection. 

The Pneumonic Type. — To Baccelli we owe the demonstration 
of a class of estivo -autumnal fevers of pernicious character, 
which, in their symptomatology, simulate pneumonia. The chief 



156 ESTIFO- AUTUMNAL MALARIA 

symptoms are cough, pain in the side, dyspnoea and the expec- 
toration of blood-stained sputa. Percussion shows dullness over 
the affected lung, and auscultation coarse, sibilant rales. The 
condition is not a true pneumonia, but is due to congestion 
brought about by the stoppage of the lung -capillaries by the 
parasites and their products. I am indebted to Major Charles 
Richard, surgeon of the United States army, for the following 
interesting example of this form of estivo- autumnal fever: 

"The patient, a soldier, gave no history of a previous mala- 
rial attack. He had suffered for some days from fever, but had 
no chills. Had much pain in the chest, a cough with expectora- 
tion, and some vomiting. The maximum temperature was 104° 
F., but there was no regularity in the curve. The man looked 
very sick and was the picture of acute lobar pneumonia. Physi- 
cal examination showed a general bronchitis. The spleen could 
be felt below the ribs. The examination of the blood showed 
numerous "ring-forms" of the estivo -autumnal parasites, and 
treatment with quinine resulted in recovery." 

The Bilious Form ("Subcontinua bilosa").— There are certain 
cases of pernicious estivo -autumnal malaria which present a com- 
plex of symptoms in which jaundice and the vomiting of bile- 
stained fluid are most prominent. These cases are usually attended 
by a more or less continuous fever, which may be greatly above 
normal. The attack is generally characterized in the beginning 
by a tertian or quotidian paroxysm, most frequently a tertian, but 
the temperature soon becomes remittent or almost continuous. 
The skin is markedly jaundiced, the fasces deeply colored by bile, 
and the urine of a deep brown or even green color. Epistaxis is 
rather common, and hematemesis often occurs. The patient is 
either apathetic and hard to rouse or is delirious. Vomiting 
is often frequent and severe, and epigastric pain and hiccough is 
present. If untreated this form of the disease is usually fatal. 
If the proper therapeutic measures are instituted, recovery is gen- 
erally the result, although cases occur which prove fatal despite 
all therapeutic efforts. 

Of the very rare forms of pernicious malarial fevers may be 
mentioned the syncopal form, noted by Sternberg, characterized by 
attacks of syncope upon exertion during the sweating stage or 
period of deferrescence of the fever; the exanthematous form, 
characterized by the occurrence of a scarlatinaform rash upon the 
skin during the paroxysms, followed by desquamation; and the 



IMPORTANCE OF BLOOD EXAMINATION 157 

pleuritic form, characterized by intermittent attacks of sharp pain 
in the side, a dry cough, and, on auscultation, friction sounds. 

EXAMINATION OF THE BLOOD IN THE PERNICIOUS FORMS OF ESTIVO- 
AUTUMNAL MALARIA 

The examination of the blood during an attack of pernicious 
malarial fever will almost invariably result in the demonstration 
of large numbers of the estivo- autumnal parasites. In no form 
of malarial fever are the parasites so numerous in the peripheral 
blood as they are in the pernicious estivo -autumnal fevers. Often 
a single field will contain from ten to twenty infected corpuscles. 

The findings in the blood vary somewhat, according to the 
period of time in which the examination is made, and according 
to the type of fever present. 

In a case of regularly intermittent pernicious estivo -autumnal 
fever, if the blood be examined at the acme of the paroxysm, the 
parasites present will be mostly of the unpigmented variety, while 
if the blood be examined during the intermission or one or two 
hours before the beginning of the paroxysm, the pigmented forms 
of the estivo -autumnal parasite will be found. At whatever time 
the blood is examined, however, it will be found that the parasites 
are all approximately in the same stage of development. 

On the other hand, if the blood of cases suffering from per- 
nicious estivo -autumnal fever, in which the temperature curve is 
irregular, or almost continuous, be examined, it will be found that 
both unpigmented and pigmented parasites will be present, at 
whatever period the blood be examined. 

A few words in regard to the importance of the examination of 
the blood in all cases residing in or coming from malarious 
regions, whenever there is a shadow of a doubt regarding the 
disease present: As has been shown, the pernicious malarial 
fevers present themselves in so many disguises, and exhibit so 
often so many atypical symptoms, that even the most acute clinical 
diagnostician may be entirely deceived regarding these cases. 
The one scientific and entirely satisfactory way of diagnosing any 
form of malarial fever is by the microscopical examination of the 
blood; it consumes but little time, is absolutely conclusive in its 
results, and, better than all, it may save the life of the patient 
entrusted to the physician's care. It should never be neglected in 
regions in which the estivo -autumnal fevers are prevalent, as it is 



158 ESTIVO- AUTUMNAL MALARIA 

in these fevers that its value is greatest. The fact should ever 
be held in mind that any estivo - autumnal fever may become per- 
nicious, and that the longer it remains unrecognized and untreated 
the greater the chances of its becoming so, and the greater the 
danger to the patient. Ignorance of the use of the microscope is 
no excuse for an omission which may cost a human life. 

In illustration of this I have in mind the case of a soldier, 
believed to be suffering from acute catarrhal jaundice. His symp- 
toms, upon entering the hospital, were so typical of this con- 
dition that the physician in charge delayed the examination of 
the blood for several days. During this time the patient ran an 
irregular temperature, never above 101° F., became very much 
jaundiced and finally lapsed into a semi -comatose condition. At 
this time the blood was examined and was found to be literally 
loaded with quotidian estivo -autumnal parasites. The most ener- 
getic treatment was at once instituted, but despite all that could 
be done the patient died in a few hours. Without doubt this 
man's life could have been saved had the blood been examined 
earlier, before the intense malarial intoxication had occurred. It 
is in such cases as this that the microscope becomes a life-saving 
agent more powerful than the surgeon's knife or the thera- 
peutist's art. 



CHAPTER XV 

LATENT AND MASKED ESTIVO- AUTUMNAL MALARIAL FEVERS — 
SUBCONTINUED ESTIVO- AUTUMNAL MALARIAL FEVERS— COM- 
BINED INFECTIONS. 

Latent and Masked Fevers.— The subject of latent and 
masked forms of the estivo- autumnal malarial fevers has not 
received the attention and study which it deserves. If such a 
thing could be possible as the microscopic examination of the 
blood in all cases of disease, in all parts of the world, it is safe 
to say that the number of cases proving to be due to the 
presence in the blood of the malarial parasites and diagnosed as 
other disease processes would be so astounding as to be almost 
unbelievable. 

In latent and masked estivo -autumnal fevers we include all 
cases in which the estivo -autumnal parasites may be demon- 
strated in the blood, but in which either no clinical symptoms 
are present or the symptoms which are present are atypical in 
character. 

A still closer definition of these terms may be made as 
follows : 

a. Latent estivo -autumnal malarial fever, in which the par- 
asites can be demonstrated in the blood, and no clinical symp- 
toms of any disease are present. 

b. Masked estivo-autumnal malarial fever, in which the par- 
asites are present in the blood, but the symptoms present are 
those of another disease, or are atypical. 

In the first-named class occur those cases discovered acci- 
dentally through an examination of the blood for some other 
purpose. Such cases have shown absolutely no symptom of 
malarial fever or other disease, yet numerous parasites may be 
found in the blood. I can recall a large number of cases in 
soldiers who have had their blood examined as a routine 
measure, in which the estivo-autumnal parasites were found, 
although there were no symptoms of the disease present. 

As a rule, in such cases, the number of parasites is com- 
(159) 



160 ESTIVO- AUTUMNAL MALARIA 

paratively small, but there may be much free pigment present 
and numerous pigmented leucocytes. In blood from the spleen 
in these latent cases the entire human cycle of the estivo- 
autumnal parasites can be followed. 

The tertian estivo - autumnal parasite is the most common 
form found in such cases, although the quotidian form is by no 
means rare. The only explanation of the fact that the develop- 
ment of the malarial parasite may not, for a considerable period 
of time, be accompanied by clinical symptoms is either that 
the parasites are present in too small numbers or that the in- 
dividual infected is very resistant to the action of the malarial 
poison. 

The length of time during which such a latent infection may 
exist is as yet undetermined, but it is probable that in some 
cases it may be for many weeks. I recall one case in which 
the estivo -autumnal parasites were found in the peripheral blood 
for six weeks before a paroxysm occurred, repeated blood- 
examinations being made during that time. I can recall many 
cases in which the parasites were found for from seven to four- 
teen days before clinical symptoms appeared. 

The second or masked estivo -autumnal malarial fevers con- 
stitute a much larger class of cases, and their recognition is of 
the utmost importance from a practical point of view. 

Such cases very often present no rise of temperature, and, 
in fact, the temperature is often subnormal. Nervous symptoms, 
such as slight headache, vertigo, neuralgias of various parts of 
the body, etc., or symptoms referable to some other disease may 
be present, as diarrhoea, acute or chronic dysentery, pneumonia, 
typhoid fever, etc. 

It should always be borne in mind, in treating diseases in 
localities in which the estivo -autumnal parasites are prevalent, 
that some of the most pernicious forms of these fevers are unac- 
companied by definite paroxysms or a rise of temperature, and 
that the temperature is not rarely subnormal. I recall a fatal 
case of quotidian estivo -autumnal fever in which the temperature 
never rose above 99° F., and in which the few symptoms present 
were those of an acute hepatitis. Examination of the blood, a 
few hours before death occurred, showed large numbers of quo- 
tidian estivo -autumnal parasites, and the findings at autopsy 
were typical of death from pernicious malarial fever. 

I would it were possible to impress upon every practitioner 



MICROSCOPICAL EXAMINATION OF BLOOD 161 

the absolute unreliability of clinical symptoms in many cases of 
estivo- autumnal malarial fever, so far as diagnosis goes, and the 
infinite importance of a microscopical examination of the blood 
in all cases of disease occurring in malarial regions. 

As an illustration of this I will quote from the record of my 
examinations in the U. $. Army General Hospital at San Fran- 
cisco, Cal. By order of Colonel Girard, the commanding officer, 
every case entering this hospital has a blood examination made, 
whether or no clinical symptoms of malaria are present. For a 
period of nine weeks fifty-six cases were found, none of which 
presented any symptoms of malarial fever, yet in which the 
peripheral blood contained the malarial parasite. 

An analysis of these cases is of interest. Thirty -seven were 
infections with the estivo -autumnal parasites, while nineteen 
were infections with the benign tertian parasite. Of the infec- 
tions with the estivo -autumnal parasites, twenty -four were infec- 
tions with the tertian estivo -autumnal parasites and thirteen with 
the quotidian estivo -autumnal parasites. 

The thirty-seven cases showing the estivo- autumnal parasites 
in the blood were diagnosed, from the clinical symptoms present, 
as follows: chronic dysentery, sixteen cases; chronic diarrhoea, 
five cases; chronic gastritis, one case; phthisis pulmonalis, five 
cases; bronchial asthma, one case; undiagnosed, nine cases. 

From the above it will be seen how little faith can be placed 
in clinical symptoms in many of these cases, and how important 
an examination of the blood is in all cases of disease. 

It may be said in passing that chronic diarrhoea or dysentery 
is very commonly associated with the malarial fevers in soldiers 
returning from the Philippine Islands, and a very marked im- 
provement in the intestinal symptoms almost always follows the 
treatment of the malaria with quinine. 

In many cases symptoms of a complicating disease will 
entirely mask those of estivo-autumnal fever, and only an exam- 
ination of the blood reveal the malarial element in the case. 
This is especially true in cases complicated with pneumonia and 
typhoid fever. 

SUBCONTINUED OR REMITTENT ESTIVO-AUTUMNAL MALARIAL 

Fever. — Certain cases, both of tertian and quotidian estivo- 
autumnal fever, instead of presenting distinct paroxysms, sepa- 
rated by an intermission, run a more or less continuous or 
slightly remittent course. I have already discussed the various 



162 ESTIVO- AUTUMNAL MALARIA 

ways in which an intermittent malarial fever may become con- 
tinuous or remittent, but will briefly recapitulate here: 

1. The paroxysms may be prolonged so that they overlap 
each other, thus causing a remittent temperature curve. 

2. The paroxysms may anticipate, one beginning before the 
preceding one ends. 

3. The paroxysms may be duplicated. 

4. By a mixed infection of the quotidian and tertian estivo- 
autumnal parasites. 

In these remittent or subcontinuous forms of the estivo- 
autumnal fevers, the generation of parasites causing the original 
attack is seldom to be demonstrated ; but in mixed infections 
both forms of the parasites may usually be easily demonstrated 
in the blood. It is these forms of malarial fever which are so 
often mistaken for typhoid fever or septicemia, especially by prac- 
titioners in localities where the estivo- autumnal fevers are rare. 
These are the forms of malaria which were supposed by many 
surgeons during the war with Spain to be present in the southern 
camps, whereas, in reality, the cases so diagnosed were typhoid 
fever. If there is one thing in the medical history of this coun- 
try which should teach the profession the folly of diagnosing the 
malarial fevers by the symptoms alone it is the experience of our 
armies in the camps throughout the South during 1898. 

Symptoms. — It is but rarely that a case of remittent or sub- 
continuous estivo -autumnal fever is observed for a period of 
time sufficient to gain an adequate idea of its symptoms and 
course, as quinine is generally given at the beginning and the 
attack cut short. In cases, however, which have been studied, 
the symptoms have been found to be very variable and often 
inconstant. The prodromal symptoms are general weakness 
and malaise, headache, loss of appetite, etc. The attack usually 
begins without a chill, although there may be slight chilly sen- 
sations or "creepy feelings." The patient's appearance is often 
very suggestive of typhoid, the face being flushed, the eyes 
brilliant, the conjunctivas inflamed, the skin hot and dry, the 
headache very severe, and general pains present in the back and 
limbs; the patient is often very nervous and restless, sleeping 
poorly and waking with a start, and there may be slight de- 
lirium. The tongue is dry and coated, nausea and vomiting are 
present, and diarrhoea is common; the pulse is rapid and dicrotic, 
the respirations hurried and often superficial, the abdomen often 



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SUBCONTINUED FEVER 165 

tender, and the spleen always more or less enlarged. In those 
cases which most closely simulate typhoid fever, the resemblance 
is indeed startling — epistaxis, roseolar eruption, gurgling and 
tenderness in the right iliac fossa, etc., all being present in addi- 
tion to the symptoms already enumerated. Before the discovery 
of the malarial parasites such cases caused much confusion, but 
to-day an examination of the blood will demonstrate their nature 
immediately. It is to this class of cases that the term typho- 
malarial fever has been applied, but the microscope has definitely 
proven the falsity of this appellation. There is no doubt that 
typhoid and estivo- autumnal malarial fever may coexist, but 
there is no such disease entity as typho- malarial fever. 

The temperature curve in the remittent estivo -autumnal ma- 
larial fevers is very variable, but there may usually be traced 
slight intermissions corresponding to the ending of the par- 
oxysms. Sometimes, however, the curve much resembles that of 
typhoid fever, there being slight daily remissions; this is espe- 
cially true of the subcontinued fevers due to the quotidian estivo- 
autumnal parasite. The chart shown is fairly typical of such a 
fever. (Chart No. 16.) 

The examination of the blood in these fevers shows the same 
parasites which cause the more regular forms of estivo -autumnal 
fever. As a rule, the parasites are fairly numerous and are gen- 
erally in various stages of development. 

Besides the typhoidal types of remittent malarial fever, vari- 
ous other forms have been described, as the bilious, pneumonic, 
etc., but such a classification is loose and unscientific and unde- 
serving of special consideration. The point to be remembered 
is that there occur many forms of estivo -autumnal malarial fever 
which pursue a more or less remittent or continuous course as 
regards temperature, and resemble clinically other febrile pro- 
cesses, and that the only way of quickly and satisfactorily diag- 
nosing them is by the microscopical examination of the blood. 

Duration of Remittent or Subcontinued Estivo -autumnal Fever. 
— If untreated the fever may continue for several weeks; but, as 
a rule, spontaneous cure or death occurs within three weeks. 
These fevers are apt to become pernicious at any time and death 
may occur suddenly. If properly treated a cure is usually 
effected within a week, but some cases are very resistant to 
quinine, and may persist for eight or ten days. 

Combined Infections. — The estivo -autumnal parasites may be 



166 ESTIVO - AUTUMNAL MALABIA 

present in the blood in conjunction with the benign tertian or 
quartan parasites, or with each other. In such combined infec- 
tions the temperature chart is apt to be irregular or remittent; 
but very often the tertian parasite may be associated in small 
numbers with the estivo- autumnal parasites without in the least 
affecting the course of the temperature. If, however, the tertian 
or quartan parasites are present in sufficient numbers to influence 
the temperature, some very peculiar temperature curves may be 
obtained. Chart No. 17 is a beautiful illustration of such a case, 
in which the estivo -autumnal and the tertian paroxysms both 
occurred independently of one another, as was shown both by the 
chart and the examination of the blood. 

Importance of the Examination of the Blood in all 
Diseases in Malarial Localities. — I have already spoken of 
the importance of blood -examinations in all malarial cases, but 
wish still further to emphasize their importance in all diseases 
occurring in malarial localities and in all patients coming from 
such localities. I speak of this matter not from theoretical knowl- 
edge, but from practical experience. I can recall more than one 
instance in which a single blood- examination saved a human life, 
in all probability, and it is because of such facts that I urge upon 
every practitioner of medicine the importance of the microscope 
in the practice of his profession. The malarial fevers are most 
insidious and most destructive diseases, and this is especially 
true of the estivo -autumnal malarial fevers. 

In the latent cases the examination of the blood is our only 
means of diagnosing the disease. Such an examination, if posi- 
tive, enables us to combat the disease before the clinical symptoms 
have appeared, and thus saves the patient much discomfort and 
danger; in the masked cases the microscope, again, is our only 
hope, and a positive examination enables us to treat the malaria 
and sometimes save a life which might otherwise have been 
sacrificed. In the remittent and subcontinued forms the micro- 
scope and quinine are our diagnostic resources. Quinine is slow 
and not always sure ; the microscope is quick and absolutely 
reliable, and a positive examination enables us to diagnose the 
disease from typhoid fever and apply the proper treatment. 
Had every surgeon during the Spanish war owned a micro- 
scope, and known how to use it, hundreds of lives would have 
been saved; the great typhoid epidemics would have been, in 
large part, prevented, and health and life would have reigned 



LATENT AND MASKED INFECTIONS 167 

instead of disease and death. This is not a flowery pen picture, 
but the statement of actual fact, for if the first cases of typhoid 
had been recognized and the proper precautions taken, there 
would have been no great epidemics such as devastated nearly 
all our southern camps. A clear understanding of the nature 
of the estivo- autumnal malarial fevers, together with a knowl- 
edge of microscopy sufficient for the recognition of the parasites 
causing such fevers, should form part of the armamentarium 
of every physician. 

Note. — Since writing the section upon latent and masked estivo -autumnal 
fever, I have kept a record of the cases in which malarial parasites were pres- 
ent in the blood, but the diagnosis other than malaria, and have, in nine 
months, at the United States Army General Hospital at San Francisco, found 
one hundred and seventy-two such cases. These may be divided as follows : 
Tertian infections, thirty-six; quartan infections, one; estivo -autumnal infec- 
tions, one hundred and thirty-one. Of the one hundred and thirty-one estivo- 
autumnal infections, one hundred and two were due to the tertian estivo- 
autumnal parasite and twenty-nine to the quotidian parasite. Forty-three of 
these cases were diagnosed as chronic dysentery, fifteen as chronic diarrhoea, 
in thirty-four no diagnosis was recorded, while the remaining thirty-nine cases 
were variously diagnosed. In none of these cases were typical symptoms of 
malarial fever present and it was only by the examination of the blood that 
it was possible to diagnose the condition. From this large number of cases 
it will be seen how important an examination of the blood is in all cases of 
disease. 



CHAPTER XVI 

COMPLICATIONS AND SEQUELS 
COMPLICATIONS 

Like all other acute disease processes, the estivo- autumnal 
malarial fevers may be complicated by, or associated with, other 
diseases; but the old idea, first advocated by Boudin, that these 
complications were due to the malarial poison, has long since 
been abandoned. The malarial parasites are not the cause of a 
pneumonia accompanying malarial fever, nor of a typhoid which 
may be coexistent with it; in each case the complicating disease 
is due to its specific organism, and though the course of either 
disease may be more or less affected by their association, yet its 
etiology remains unchanged. In other words, there is no such 
thing as a peculiar form of pneumonia or typhoid due to the 
estivo-autumnal parasites. 

I shall classify the diseases which may complicate the estivo- 
autumnal malarial fevers under the following headings: 

1. Diseases of the Nervous System. 

2. Diseases of the Respiratory System. 

3. Diseases of the Circulatory System. 

4. Diseases of the Genito-urinary System. 

5. Diseases of the Gastro-intestinal Tract. 

6. Miscellaneous. 

1. Diseases op the Nervous System.— Coincident with the 
estivo-autumnal fevers there may occur attacks of acute mania, 
and such cases have been described by Yanirris,* but this com- 
plication is very rare. Hysteria is not a very uncommon com- 
plication in nervous women or even in men, and, as in hysterical 
attacks in general, the symptoms complained of vary greatly in 
character and severity. Paraplegia and hemiplegia may rarely 
complicate these fevers, and neuroses of various kinds are not 
uncommon. Meningitis may also occur. 

2. Diseases of the Respiratory System. — Both lobar and 

*La. Med. Orient., 1898., II., 6. 
(168) 



PNEUMONIA, BRONCHITIS AND TUBERCULOSIS 169 

lobular pneumonia occur as complications, the first being by no 
means a rare complication. Early observers held that the pneu- 
monia accompanying malaria was directly due to malarial poison; 
but recent investigations have conclusively proven that the 
malarial parasites per se are unable to produce a true pneu- 
monitis. The pneumonia complicating malaria will always be 
found, upon bacteriological examination, to be due to the diplo- 
coccus pneumonia}. 

I have already described the form of pernicious estivo - 
autumnal fever in which the symptoms are chiefly referred to 
the lung and are identical with those of lobar pneumonia. 
The condition present in these cases is due to a localization of 
the parasites in the lung capillaries. Microscopical examination 
of the lung, in such cases, shows that the lesions present differ 
widely from those common to lobar pneumonia. 

Pneumonia may complicate the malarial infection at any time, 
and may develop suddenly or insidiously. The course of the pneu- 
monia is generally but little altered, although the disease is apt to 
assume a more severe type than when it occurs alone. Pneumonic 
symptoms may entirely mask the malaria, or, on the other hand, 
may be so slight as to be masked by the malarial infection. 

The prognosis in pneumonia complicating estivo- autumnal ma- 
laria is always very grave, many cases proving fatal. The mortality 
is stated by Ascoli to be as high as 60 to 78 per cent in patients 
who have had repeated estivo -autumnal attacks. Death may occur 
from thirty -six to seventy -two hours from the initiation of the 
attack. 

In cases which recover, the convalescence is very slow, resolu- 
tion being greatly delayed. An empyema may result in rare 
instances. Not rarely the affected portions of the lung become 
fibroid, and a chronic fibroid pneumonia results, or a bronchiec- 
tasis appears. 

Pneumonia septicemia as complicating malaria, has been de- 
scribed by Bignami, Marchiafava, and Nazari. 

Acute bronchitis is a very common complication of the estivo- 
autumnal malarial fevers, being observed in about 40 per cent of 
the cases. It may be very persistent and often very markedly 
weakens and exhausts the patient. 

Tuberculosis. — The old belief that tuberculosis and malaria 
could not exist to any extent together has been exploded. We 
now know that both diseases are very commonly associated, and 



170 ESTIVO- AUTUMNAL MALARIA 

that even fatal cases of estivo- autumnal malaria may occur in 
patients suffering from active tuberculosis. Marchiafava and 
Bignami have reported a very interesting case of this kind. 
Marchiafava claims that "if the malarial infection attacks organ- 
isms affected by tuberculosis, the latter is not arrested, but 
acquires a tendency to spread, and produces miliary tuberculosis." 
The same authority states that "according to our experience, 
malarial cachexia does not predispose to tuberculosis, as do other 
cachexias." 

Pleurisy is a somewhat rare complication, and when it occurs 
pursues the same clinical course as is usual. 

If quinine be administered to a patient suffering from any of 
the complications mentioned it will be followed by the cessation 
of the malarial symptoms, and the complicating process will run 
its usual course. 

The diagnosis of estivo -autumnal malaria, when its symptoms 
are masked by complications, is only to be made by the micro- 
scopical examination of the blood. 

3. Diseases of the Circulatory System.— Any of the 
organic diseases of the heart which may be present at the time 
of an estivo -autumnal infection will complicate it, and often in 
such cases the prognosis is exceedingly grave. 

Acute endocarditis may occur as a complication and the ulcer- 
ative form of the disease may follow a pneumonic complication. 

Functional disorders of the heart are very common complica- 
tions of the estivo -autumnal malarial fevers. A slow pulse during 
convalescence is common, sometimes counting but forty to the 
minute. 

4. Diseases op The Genito- urinary System. — Nephritis is 
one of the most common complications of these fevers, and occurs 
in about 3 per cent of the cases. As a rule, the nephritis is an 
acute one, and generally subsides shortly after the cessation of the 
malarial attack. As nephritis is as much a consequence of malarial 
infection as it is a complication, I have considered it more fully 
in that portion of this chapter treating of the sequelae of the 
estivo -autumnal fevers. 

Orchitis and epididymitis not so very rarely occur as complica- 
tions, but a history of gonorrhea is usually to be obtained. Some 
authorities have claimed that there is an orchitis due to the 
malarial poison, i.e., a malarial orchitis. I have never observed 
a case of this kind, although I have seen several cases of orchitis 



GASTRO- INTESTINAL COMPLICATIONS 171 

complicating malaria, but there was invariably a venereal history- 
obtainable. Personally I do not believe that a malarial orchitis 
or epididymitis ever occurs. 

5. Diseases of the Gastro- intestinal Tract. — Various 
disorders of the gastro -intestinal tract may complicate the estivo- 
autumnal fevers. But I shall consider only two — dysentery and 
typhoid fever. Acute and chronic gastritis and enteritis are very 
common complications, and, during epidemics, cholera has occurred 
coincidently with malaria. 

Dysentery. — In patients from certain localities dysentery is a 
very frequent complication of the estivo- autumnal infections. In 
the case of soldiers returning from the Philippine Islands, as 
observed at the U. S. General Hospital, at San Francisco, 65 per 
cent showing the estivo -autumnal parasites in the blood were also 
suffering from acute or chronic dysentery. Of this percentage, 
about 10 per cent were suffering from amoebic dysentery, as evi- 
denced by the finding of the amoeba coli in the fasces. Dysentery 
complicating malaria, as I have observed it, runs an aggravated 
course, and is more apt to be fatal than when it occurs alone. 
Not infrequently the malarial infection appears to be latent, the 
dysenteric symptoms only being present. In Chapter XX, I have 
considered the diagnosis of such cases, but would repeat here that 
the blood of every case of dysentery coming from a malarial 
locality should be carefully examined for the malarial parasites. 
The administration of quinine in cases of estivo -autumnal malaria 
complicated by dysentery not only removes the malarial infection, 
but, in many instances, the dysentery improves and a return to 
health is more rapid. The explanation of this fact is not hard 
to find. We know from pathological study that the mucous 
membrane of the large intestine, as well as the small, is generally 
invaded by the malarial parasites, which invasion must necessarily 
injure the vitality of the tissues. Eemoval of the parasites by 
quinine obviously aids the tissues in regaining their normal con- 
dition and thus indirectly improves the dysenteric disease. 

Typhoid Fever. — The simultaneous occurrence of typhoid and 
malarial fevers is a subject of much interest to investigators, one 
which has given rise to much controversy, and has evoked many 
varying opinions from eminent authorities. The only cases in 
which we can say that such a combination exists are those in 
which the plasmodia of malaria can be demonstrated in the blood 
and, at the same time, some substantial proof of the existence of 



172 ESTIVO- AUTUMNAL MALARIA 

typhoid, as the separation of the bacilli from the excreta or a 
positive reaction to the Widal test, can be shown to exist. Such 
recorded cases are markedly few in number, if we consider the 
large number of cases in which the diagnosis of typho- malarial 
fever is made. In a recent publication, Dr. Irving Phillips Lyon* 
has collected all the published cases of combined typhoid fever 
and malaria on record, which have been proved to be such by the 
tests mentioned. These numbered only twenty -nine in all, most 
of them being cases of combined typhoid and tertian malarial 
fevers, and a few combined typhoid and estivo- autumnal fevers. 

The old theory, announced by Woodward, that the conjunction 
of these fevers produced a typical disease, which he called typho- 
malaria, has been abandoned, and we now know that even the 
combination of these diseases is very rare. I have only observed 
five instances of such combined fevers in over four thousand cases 
of fever in which the blood was examined microscopically. Of 
these five cases, four were combined infections of typhoid and the 
estivo -autumnal malarial fevers, while one was a combined infec- 
tion of typhoid and quartan malarial fever. The latter case is, I 
believe, the only one on record in which the quartan parasite was 
demonstrated in the blood. As a rule, the malarial attacks occur 
during convalescence from typhoid; but they may occur during 
the acute stage, or even at the very beginning. The symptoma- 
tology of the typhoid in such cases is but little altered, and there 
is nothing at all characteristic about the combined infection. 

In such cases the malaria is almost always of long standing, 
and the attacks complicating typhoid are generally relapses. 

The two following cases of combined typhoid and estivo- 
autumnal malarial fevers are interesting and instructive. The 
first, reported by Be vans, t occurred at the U. S. A. General 
Hospital at San Francisco, Cal. The following is the clinical 
history of the case, as given by Acting Assistant Surgeon Be vans, 
together with my report upon the examination of the blood: 

"Corporal R. M., Co. K, 29th U. S. V. Inft., aged 21, 
born in Tennessee, was admitted on October 3, 1899. The man 
lived in his native state until enlistment in the Fourth Tennessee 
Volunteer Infantry in the fall of 1898. He then served in Cuba, 
and during his first service had a few light chills, which con- 
tinued after his return home and until his reenlistment in August, 

*"Am. Journal of the Medical Sciences," January, 1899. 
t"New York Medical Journal," February 10, 1900. 



TYPHOID FEVER 173 

1899. At this time he was apparently well. The chills appeared 
again at Fort McPherson, where he stayed about a month, and 
continued irregularly up to the time of his present sickness. En 
route to the Presidio, where he arrived October 1, he was confined 
to his bed with headache, constipation, general malaise and light 
chills. He had not, previous to that time, been on sick report. 
After three days in quarters in camp he was sent to the General 
Hospital. As he was brought into the ward he looked pale, 
emaciated and cold. His temperature was 102.4 °F., respiration 
22, and pulse 94. His tongue was coated, the abdomen tender, 
the liver and spleen were somewhat enlarged. His mental condi- 
tion was dazed. By October 7 rose spots had developed, and he 
was in an active delirium. He had involuntary passages of urine 
and feces. Light chills occurred daily after the 6th. On the 
11th the chill was prolonged and severe. Malarial parasites were 
first found in the blood on that day. Quinine was then admin- 
istered in large doses, and the last chill was observed two days 
later. Delirium continued until the 25th. The temperature curve 
and symptoms after the 13th were those of typhoid fever. The 
temperature reached normal- on the 29th and slow convalescence 
has taken place. 

"Examination of the blood: October 4. Examination for 
the Plasmodia of malaria, negative. There are some leucocytes 
containing pigment. Widal test, negative. 

"October 8. Malaria, negative. 

"October 11. Numerous ring-forms of the quotidian estivo- 
autumnal parasite present. These are small, circular in form, 
somewhat refractive, the pigment consisting of from one to two 
small, almost black, specks. Not amoeboid. The corpuscles con- 
taining the organisms are dark olive -green in color and shrunken. 
A few are crenated. Widal test, negative. 

"October 13. Malaria, negative. Widal test, negative. There 
seems to be a slight clumping, but the bacilli remain motile. 

"November 3. Malaria, negative. Widal test, negative. There 
are a very few minute clumps, but the bacilli remain motile. 
This may possibly be a very slight reaction, but I would ordi- 
narily consider it as negative. 

"November 9. Malaria, negative. Widal test, positive. 
Marked reaction immediately. It is interesting to note that this 
is the first positive reaction obtained, and raises the question as 
to whether or not the malarial complication hindered or lessened 



174 ESTIVO- AUTUMNAL MALARIA 

the power of the blood to give a reaction. This may possibly be 
the explanation, although in the few eases of malaria complicat- 
ing typhoid which I have seen, the Widal test has always been 
responded to promptly." 

The history of the second case, observed at the Simpson 
U. S. A. General Hospital, Fortress Monroe, Va., is as follows: 

"S. J., 8th Illinois, colored, arrived at Santiago, Cuba, upon 
August 16, 1898. Had suffered from chills and fever before 
leaving the United States, but does not think that he had malaria 
in Cuba, but suffered from diarrhoea and fever. Arrived at the 
Simpson Hospital on March 16, 1899, with a diagnosis of diar- 
rhoea. Gave a history of having been sick for two weeks with 
diarrhoea and fever, but had had no chills. On the 17th he had 
a chill and his temperature rose. He suffered from headache, 
backache and nausea. Physical examination showed an enlarged 
spleen, tender abdomen, hot, dry skin and brilliant eyes. Heart 
and lungs normal. An examination was made of his blood, and 
numerous ring -forms of the tertian estivo- autumnal parasite were 
found, every field showing one or more. Quinine was at once 
administered, but as the temperature did not decline, the Widal 
test was made and a marked reaction obtained. All the typical 
symptoms of typhoid fever were present, and the course of the 
disease, after the malarial element was eliminated by quinine, was 
that of a gradually declining typhoid." 

In this case it will be seen that the malarial complication 
occurred during the acute stage of the typhoid, as the patient had 
been suffering from the fever about two weeks before his entry to 
the hospital. A study of the chart (Chart No. 18) will shov how 
little the malaria affected the course of the typhoid, and that but 
for the microscope a diagnosis could hardly have been reached. 

The recognition of such cases as these is very essential, espe- 
cially in treating fevers in tropical countries. The administration of 
quinine is proper in malarial fever, but in typhoid fever it is almost 
criminal, as grave mischief is often the result of such treatment. 

Thayer* has very aptly discussed this point as follows: "The 
mere use of the term typho- malarial fever has indicated to many 
the advisability of the administration of quinine, and not infre- 
quently this drug is used for days and for weeks in cases of 
uncomplicated typhoid fever in doses which cannot but be inju- 
rious to the patient. This is a matter of really grave importance. 

*" Lectures on the Malarial Fevers." 



SEQUELM 175 

It is one of the positions in which the physician actually has 
done and does do, to-day, really serious harm to his patient. There 
is no excuse for cinchonizing an individual with continuous fever 
who, after three or four days, shows no change in the symptoms, 
while the blood is free from malarial parasites." 

In support of Thayer's statement, I may say that I have seen 
forty grains of quinine administered every day for four weeks in 
cases of simple typhoid fever which were supposed to be malarial 
in nature, and it is not too much to say that such treatment is 
criminal and cannot be too strongly condemned. 

6. Miscellaneous. — Erysipelas sometimes complicates the 
estivo- autumnal fevers, and in patients debilitated by prolonged 
malarial attacks is apt to be followed by streptococcic septicemia. 

Insolation may complicate estivo -autumnal malaria and may 
aid in precipitating a pernicious attack. To Sternberg belongs 
the credit of first recognizing this complication, which is a most 
important one to guard against in the tropics. It is now gen- 
erally admitted that an individual who has suffered from re- 
peated attacks of malaria is much more sensitive to the sun's 
rays than one who has not, and that insolation is very apt to 
occur in such cases. 

Acute rheumatism, sciatica, tonsilitis, parotitis, various skin 
eruptions, and variola have all been reported as complicating the 
estivo -autumnal malarial fevers. 

SEQUELiE OF THE ESTIVO-AUTUMNAL MALARIAL FEVERS 

Properly speaking, the sequela? of a disease are those affec- 
tions which develop after the disease itself has ceased, but there 
are certain affections which arise during attacks of the estivo - 
autumnal fevers, which persist after the malarial symptoms have 
disappeared. These must be regarded as due to the effect of the 
malarial poison upon the system, and must, therefore, be re- 
garded as sequelae of the disease. 

The various sequelae may be divided as follows : 

1. Diseases of the Nervous System. 

2. Diseases of the Circulatory System. 

3. Diseases of the Digestive System. 

4. Diseases of the Genito- urinary System. 

5. Diseases of the Glandular System. 

6. Diseases of the Organs of Sense. 



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178 ESTIVO- AUTUMNAL MALARIA 

1. Diseases op the Nervous System. — The nervous affec- 
tions which may occur with or follow the estivo- autumnal fevers 
are very numerous, and are especially common in the pernicious 
forms of the disease. The blocking of the capillaries of the 
cortex of the brain by the malarial parasites and free pigment 
often leads to evanescent local paralyses, which disappear under 
proper treatment. In some cases, however, they may remain for 
months. Such a case I recall in which a paresis of one side of 
the face developed during a severe estivo -autumnal attack, which 
persisted for two months after the fever was apparently cured. 

Not uncommonly, after severe attacks, the mind seems to be 
unnaturally inactive, memory being defective, and sometimes an 
almost stuporous condition may be present. 

Various psychical disturbances may occur, and aphasia is not 
very uncommon, 

Melancholia, mania, and delusional insanity sometimes follow 
the estivo -autumnal malarial fevers. In some cases the mental 
depression occurring with and following the paroxysms is very 
noticeable, and it is a very common thing to have patients who 
have suffered from attacks of these fevers complain of having 
"the blues," or of ill -defined forebodings. An exaggeration of 
this condition becomes melancholia, which is not so very rare. 
I have observed cases of mania, melancholia, and delusional in- 
sanity in soldiers returning from the tropics, which were un- 
doubtedly sequela? of severe repeated attacks of the estivo- 
autumnal malarial fevers. 

Multiple neuritis has been described as following estivo- 
autumnal malaria, by Gowers, Raymond and Jourdan. Glogner 
has studied very exhaustively several cases of polyneuritis follow- 
ing malarial fever, the symptoms consisting of severe pain in 
the lower extremities, increased by pressure, formication, partial 
or total weakness of sensibility, and response to electrical stim- 
ulation, weakness, and edema. 

Chiarini and Bardellini have confirmed Glogner' s observa- 
tions and there can be no doubt that these cases of polyneu- 
ritis were due to malarial infection. 

Bastianelli, Bignami, and Chiarini have described cases in 
which electric chorea or "Dubini's disease" was present in estivo- 
autumnal infections. 

Neuralgia is a common sequelas of estivo -autumnal malaria, 
although it should be noted that it is not as common as is gener- 



CIRCULATORY AND OTHER SYSTEMS 179 

ally supposed. Many cases of so-called malarial neuralgias have 
in reality no connection with malaria, and the name is used simply 
as a cloak for ignorance of the true etiology of the affection. The 
regions most affected by malarial neuralgia are the face and 
lumbar region. I recall a case of very severe sciatica following 
a tertian estivo- autumnal attack, which was finally overcome by 
quinine alone. The patient had never suffered from sciatica 
before and has never had an attack since. 

2. Diseases op the Circulatory System. — Lancereaux, 
Huchard, and a few other observers have endeavored to show 
that endocarditis and arteritis may be caused by malaria, but 
their arguments are illogical, and they furnish no convincing 
proof of the truth of their assertions. When these diseases 
occur with the estivo -autumnal fevers, they are complications 
and not sequela?. 

3. Diseases op the Digestive System. — As a result of the 
localization of the malarial parasites in the mucous membrane of 
the stomach and intestine, a true acute or chronic ulcerative 
enteritis and the formation of gastric ulcers may occur. 

Pensuti, as quoted by Thayer, reports one case in which 
atrophy of the gastro- intestinal mucous membrane followed a 
malarial attack. From the results of a large number of autopsies 
performed upon patients dying of chronic dysentery, having suf- 
fered previously from malarial fever, I should be very much inclined 
to doubt the occurrence of such cases as that described by Pensuti, 
as even in these cases, which are certainly most liable to such 
changes, atrophy of the mucous membrane of the stomach and 
intestines, unless immediately around the dysenteric ulcers, is not 
common. 

4. Diseases op the Genito- urinary System. — Albuminuria 
is of very common occurrence along with, and following, estivo- 
autumnal malaria. A large number of authorities have investi- 
gated this subject, and I will quote their results in brief. Thayer 
and Hewitson found it present in over 50 per cent of their cases. 
Regarding albuminuria Thayer* says: "Albuminuria was much 
more frequent in estivo -autumnal fever than in the regularly 
intermittent fevers, occurring in 38.6 per cent of the latter, and 
in 58.3 per cent of the former; while casts of the renal tubules 
were found in 12.2 per cent of tertian and quartan infections, and 
in 24.7 per cent of the cases of estivo -autumnal fever." 

*"Progressive Medicine," March, 1899, p. 297. 



180 ESTIVO-AUTUMNAL MALARIA 

Rem-Pici has contributed much to our knowledge of this sub- 
ject, and he divides the albuminurias into the febrile, which occur 
with the paroxysms, or follow them at once, and the post -ma- 
larial, which occur after the malarial attack, and in malarial 
cachexia. From personal experience I believe that albuminuria 
occurs in about one-half of our cases of estivo- autumnal malarial, 
that it is most common in the tertian type of the disease, and 
that it is most common immediately after the paroxysm. 

Nephritis. — Both acute and chronic nephritis may occur as 
sequehe of estivo -autumnal malaria. 

Kelsch and Kiener* have given the subject of malarial nephritis 
much study, and have described two forms of the disease, i.e., the 
glomerular nephritis and the granular nephritis. 

The glomerular form is subdivided into acute and chronic, the 
first developing during or immediately after the acute malarial 
infection, the second during chronic infection. The clinical symp- 
toms are those of acute and chronic parenchymatous nephritis. 

The granular form is also divided into acute and chronic, the 
first developing in patients who have had numerous relapses of 
malaria, the clinical symptoms being those of subacute and chronic 
interstitial nephritis. 

Rem-Pici divides the malarial nephrites into acute and chronic. 
The acute nephritis develops either during or after estivo-autumnal 
infections, and varies in severity and duration. As a rule, the 
prognosis is good for early recovery. He finds that it is most 
common in the autumn and winter, and in young, rather than 
old people. The most of these cases end in recovery, but a few 
become chronic. 

The chronic form is a true interstitial nephritis, which may 
develop without a previous acute attack. At first it is a chronic 
parenchymatous nephritis, but later assumes an interstitial char- 
acter. It is, however, much more rare than the acute form. 

Amyloid degeneration may occur in the acute parenchymatous 
form of malarial nephritis. 

From my own observations I should say that nephritis occurs 
in at least 3 per cent of the cases of estivo-autumnal malaria, 
and casts of the renal tubules are found in at least 25 per cent 
of the cases. Very rarely death occurs during the malarial attack 
as the result of an acute nephritis, but I have never observed 
such a case. 

* "Polielinico,"1898, 197. 



DISEASES OF THE GLANDULAR SYSTEM 181 

In Santiago, Cuba, during 1898, several such cases occurred 
among the American soldiers, and were at first regarded as cases 
of yellow fever. 

Polyuria is not an uncommon sequelae of the estivo- autumnal 
fevers. I have observed a large number of such eases, and in some 
instances the condition was very extreme. Polyuria is generally 
noticed just before and after the malarial attack. In one case, 
which was reported by Clark, the amount of urine passed during 
the twenty -four hours varied from 20,000 to 25,000 cubic centi- 
meters for a period of several weeks. 

Glycosuria was once thought to be a common sequelas of this 
type of malaria, but later observations have shown that it is very 
rarely observed. 

5. Diseases op the Glandular System.— The Liver. — In 
cases which have suffered from repeated attacks of estivo- autumnal 
malaria, a condition known as hypertrophic malarial hepatitis 
develops, the organ being enlarged, sometimes enormously so, 
the perilobular tissue increased in amount, and the capillaries 
markedly dilated. This condition, however, does not cause marked 
disturbance in the functional activity of the organ, and no clinical 
symptoms are present which are characteristic. 

Cirrhosis of the Liver. — Typical cirrhosis of the liver is, I 
believe, never the result of estivo -autumnal malaria. It may very 
rarely be present, but when it is, I believe it to be due to some 
other cause. That this is so, is evidenced by the fact that cirrhosis 
of the liver is no more common in malarial localities than it is in 
immune districts. 

The Spleen. — In chronic malarial cachexia, due to the estivo- 
autumnal parasites, the spleen becomes often very greatly en- 
larged, and to this enlargement are due certain interesting sequela? 
of the disease. 

Floating Spleen. — In rare instances the enlarged spleen, by its 
weight, sinks into the abdominal cavity, the ligaments which hold 
it in place become stretched, and the organ can be felt as a 
movable mass through the abdominal walls. The symptoms pro- 
duced are pain upon moving and reflexed disturbances, as head- 
ache, nausea, vomiting, etc. 

Rupture of the Spleen. — The enlarged spleen is generally very 
soft and friable in acute infections, and very rarely this leads to 
rupture of the organ. This result may be induced by blows, 
falls, from retching in vomiting, or simply from sudden move- 



182 ESTIVO -AUTTJMNAL MALARIA 

ments of the body. The symptoms are sharp, lancinating pain 
in the left side, and the usual symptoms of collapse due to hem- 
orrhage. Death may occur within a few moments, or a day, or 
even two, may pass before the fatal ending, depending entirely 
upon the amount of laceration present. 

Abscess of the Spleen. — Laveran has described the formation 
of abscesses within the spleen, which he has termed malarial 
abscesses. Without doubt such abscesses have resulted from 
bacterial invasion, as the malarial parasite is not a pyogenic 
organism. 

6. Diseases of the Organs op Special Sense.— The Eye.— 
Affections of the eye are not very uncommon as sequelse of the 
estivo- autumnal fevers, especially in the tropics. I shall de- 
scribe briefly the most important. 

Amaurosis. — In severe pernicious estivo -autumnal malaria, 
amaurosis sometimes occurs, and is very often accompanied by 
other nervous symptoms. It is usually bilateral, and may last 
from a few moments to hours. In rare instances permanent 
blindness may result. It is most common with the tertian estivo- 
autumnal fever. 

Suppurative Choroiditis. — A case of this kind which termi- 
nated in destruction of the eye has been described by Pennoff. 

Iritis and Keratitis. — A few observers, notably Seluck, Van 
Milligen, and Kip have described cases in which iritis and kera- 
titis have developed during estivo -autumnal attacks. Among 
the ocular changes which accompany chronic estivo -autumnal 
malaria may be mentioned optic neuritis, described by Sulzer; 
atrophy of the optic nerve, described by Bull; albuminuric reti- 
nitis described by Poncet, and effusion into the vitreous, de- 
scribed by Sulzer and Seely. 

The Ear. — Certain affections of the ear have been ascribed 
to malaria, but only a few can be regarded as really due to 
malarial poison. These are: otalgia, intermittent in character, 
cases of which have been described by Frank, Politzer, and De 
Rossi; deafness, of intermittent character, described by Bar, 
Wolff, and Ferreri; labyrinthine vertigo, which has been well 
studied by Ferreri. 

Miscellaneous : Post -malarial Changes in the Blood. 
— The Anemia. — In the estivo -autumnal forms of malaria, the 
anemia produced by repeated attacks may be very extreme and 
also very persistent. In the tertian and quartan fevers the 



PERNICIOUS ANEMIA 183 

regeneration of the red blood -cells is very rapid as compared 
with the estivo- autumnal fevers, and in these the number of red 
corpuscles may reach a very low level. I remember several cases 
in which the number of red cells was but 900,000 per cubic mil- 
limeter, and one in which the blood- count showed but 497,000 
per cubic millimeter. As a rule the greatest reduction occurs 
during the first paroxysms. 

The hemoglobin is markedly reduced and always in about the 
same ratio as the red blood -corpuscles. 

The white cells are reduced in number as a whole, but the large 
mononuclear forms are increased in number. A leucocytosis is 
generally an indication of the presence of some complication. 

Pernicious Anemia. — The anemia following estivo -autumnal 
attacks is not always benign, but may gradually merge into a 
progressive and fatal form. Bignami, Bastianelli, and Dionisi 
have described two forms of pernicious anemia occurring after 
malarial fever. 

1. A form, resembling in its clinical symptoms, blood findings 
and pathology, the classical type of pernicious anemia. In this 
form the blood shows poikilocytosis, the presence of microcytes, 
abnormally staining red corpuscles and nucleated red cells, chiefly 
megaloblasts. 

2. The second form is most interesting, for while it is gen- 
erally fatal, the blood does not show any nucleated red cells. 
This lack of nucleated red cells is due to the almost complete 
absence of regenerative power in the blood-forming organs, and 
the condition is similar to that found after profuse hemorrhage 
from any cause. 

The latter form I have observed several times, the blood in 
the cases showing no nucleated red cells and the red cells num- 
bering from 490,000 to 590,000 per cubic millimeter. The leuco- 
cytes were about normal in number, but the polymorphonuclear 
leucocytes were relatively increased in number. The blood in 
these cases showed but a very slight degree of poikilocytosis, but 
there were great differences in the size of the red cells. 

Malarial Cachexia. — In persons who have suffered from re- 
peated attacks of estivo -autumnal malaria which have not been 
properly treated, and who live in infected localities, a cachexia 
develops, which is the result of the malarial poison. This cachexia 
is, however, curable, and sometimes simply removal of the patient 
to an uninfected locality will result in recovery. 



184 ESTIVO- AUTUMNAL MALARIA 

Patients suffering from malarial cachexia are very anemic; 
the skin is sallow; there is loss of appetite and energy, diarrhea, 
dyspnoea, emaciation and many nervous disturbances. The liver 
and spleen are always enlarged, often enormously so. The tem- 
perature usually shows a slight rise toward evening, but seldom 
reaches 102° F. This condition is very common in children liv- 
ing in malarious localities, and, unfortunately, is often overlooked 
or diagnosed incorrectly. 

Estivo- autumnal cachectics are very liable to acute infectious 
diseases, and slight injuries are apt to be followed by phleg- 
monous inflammation. Death, in the adult, rarely follows from 
the cachexia, but is the result of complicating processes. 

Examination of the blood is very often unrewarded, but occa- 
sionally a ring -form of the parasite may be found, and crescents 
and ovoid bodies may be encountered in some cases. Pigmented 
leucocytes are more common, and a diagnosis can be made from 
them, provided the observer can recognize malarial pigment. 

In closing this chapter I would call attention to the presence, 
in the tropics and in patients from the tropics, of estivo- autumnal 
malaria complicating wounds or surgical diseases. In such pa- 
tients a rise of temperature during the treating of a wound or 
after operation, will, upon examination of the blood, be found to 
be due to malarial infection, and such an examination will often 
lift a load of anxiety from the surgeon and throw light upon 
obscure cases of fever. 



CHAPTER XVII 

THE DIAGNOSIS AND PROGNOSIS OF THE ESTIVO- AUTUMNAL 
FEVERS 

Diagnosis. — Unlike the tertian and quartan malarial fevers, 
the diagnosis of the estivo- autumnal fevers is often most diffi- 
cult, and seldom easy. In making the diagnosis in this variety 
of malarial disease there are two methods which are alone de- 
serving of confidence. These are the microscopical examination 
of the blood and the therapeutic test by quinine. 

The examination of the blood is the most infallible method 
of arriving at a diagnosis and should never be neglected. The 
clinical symptoms in these cases are often so misleading, the 
periodicity of the attacks so often irregular, and the prognosis 
so grave, that to undertake a diagnosis by any other method is 
at once unsatisfactory and dangerous. The therapeutic test by 
quinine, while it is often decisive, should not be relied upon 
wholly, in these cases, as they are often very resistant to qui- 
nine, and thus the correct diagnosis of the case is long delayed, 
and the life of the patient endangered. There is but one abso- 
lutely reliable and scientific method of diagnosing the estivo- 
autumnal malarial fevers, and that is by the microscopical ex- 
amination of the blood. 

As a rule, one examination will be found sufficient; but if a 
negative result is obtained in a suspected case, repeated exam- 
inations should be made at intervals, for in many cases but few 
parasites are present in the peripheral blood, and these only at 
intervals. There undoubtedly occur cases of estivo -autumnal 
fever in which the parasites are so few in number in the pe- 
ripheral blood that every microscopical examination may prove 
negative. From personal experience, I believe that such cases 
are very, very rare, and so mild in character that they are im- 
possible to recognize clinically. I have never seen a case of 
acute estivo -autumnal infection severe enough to cause clinical 
symptoms which did not show parasites in the blood upon re- 
peated examinations. On the other hand, I have records of 

(185) 



186 ESTIVO- AUTUMNAL MALARIA 

many eases in which but very slight or no clinical symptoms 
were present, yet parasites were found in the peripheral blood. 

Among the factors to be considered in arriving at a suppo- 
sitional diagnosis of estivo- autumnal fever, may be mentioned 
the time of occurrence of the disease, as in summer and autumn, 
in temperate climates; the locality, as to whether or not it is 
malarious; the location of the dwelling of the patient, and pre- 
vious attacks; periodicity of the disease, etc. 

DIAGNOSIS OF THE DIFFEEENT TYPES OF ESTIVO -AUTUMNAL 

FEVEK 

The Quotidian Type. — The diagnosis of the quotidian type, 
when uncomplicated, is comparatively easily made, because of 
the presence, generally, of a distinct chill and the periodicity of 
the fever. The differential diagnosis of this type from that of 
a double benign tertian is impossible without the aid of the 
microscope. 

The Tertian Type. — The diagnosis of the tertian type is much 
more difficult and often impossible clinically. The chill is, as a 
rule, either absent or very slight; the paroxysms are of long 
duration, and the general symptoms are so atypical in many 
instances that a diagnosis is very difficult. I have stated that 
the temperature chart, in an uncomplicated case of tertian 
estivo -autumnal fever, is absolutely diagnostic, provided the 
temperature be taken every four hours, at least, and this is so; 
but it would be folly to wait for several days in order to arrive 
at a diagnosis in this way when ah examination of the blood, 
upon the very first day, will clear up the nature of the case at 
once. 

In this form of estivo - autumnal malaria the diagnosis should 
rest chiefly upon the results of blood examinations. 

The Pernicious Types. — In these types, so often resembling 
other forms of disease, a diagnosis in any other way than by a 
microscopical examination of the blood, is, as a rule, impos- 
sible. It is safe to say that hundreds of lives have been sacri- 
ficed to pernicious malarial fever which could have been saved 
had an examination of the blood been made. I can recall one 
case in which death followed pernicious attacks of malaria, in 
which the blood examination was delayed until too late for 
therapeutic measures to be taken, and several instances in which 



DIFFERENTIAL DIAGNOSIS 187 

death was narrowly averted by the discovery of the parasites in 
cases of unrecognized pernicious malaria. 

In all cases in which a suspicion of malaria exists the first 
thought of the diagnostician should be the microscopical exam- 
ination of the blood. 

The Irregular and Continued Estivo- autumnal Fevers. — It is 
in this class of malarial cases that the microscope is of the 
greatest value to the practitioner. These cases, which present 
anomalous clinical symptoms, and irregular or continuous tem- 
perature curves, are very difficult of recognition and are often 
mistaken for other diseases. In many of them a diagnosis, from 
the clinical symptoms, is absolutely impossible, and it is in such 
that the microscope is of the greatest aid. A few moments' 
study of the blood will often demonstrate the nature of a case 
which has baffled the diagnostic acumen of eminent practitioners 
for days. 

Upon what appearances in the blood can a diagnosis of 
estivo -autumnal malaria be made ? First, and most important, 
upon the presence of the intracorpuscular, hyalin, or pigmented 
parasites. These are best looked for during the last stage of a 
paroxysm or in the interval. Often an examination of the blood 
at the beginning of a paroxysm will result negatively, but re- 
peated examinations at intervals will generally demonstrate the 
parasites. Second, crescents and ovoid extracellular forms always 
denote an estivo -autumnal infection of some days' standing. 
Third, the presence of free pigment and pigmented leucocytes, 
provided a distinct history of chills cannot be obtained. If such 
a history is obtainable it is impossible to differentiate the type 
of malarial infection present from such appearances. 

Differential Diagnosis. — The differential diagnosis of the 
estivo -autumnal malarial fevers from other disease processes, 
which may closely resemble them, is only possible, in many 
instances, by the use of the microscope. This is especially 
true of the typically intermittent quotidian type, which, by 
reason of its temperature curve, resembles many acute diseases. 
In the tertian type of estivo -autumnal fever the characteristic 
temperature curve, if present, is alone sufficient to differentiate 
it from other diseases; but in the pernicious and irregular cases 
the differentiation is most difficult without the aid of the micro- 
scope. I shall consider separately a number of diseases with 
which the estivo -autumnal fevers are liable to be confused. 



188 ESTIVO- AUTUMNAL MALARIA 

Typhoid Fever. — There is no disease with which estivo - 
autumnal malaria has been so often confused as with typhoid 
fever. Our experience during the war with Spain is alone 
abundant proof of this assertion. At least three -fourths of the 
fevers occurring in the southern camps during 1898, and diag- 
nosed as "remittent malarial fever," were, in reality, typhoid, 
as shown by the examination of the blood and the Widal test. 
Clinically, this confusion has often much to justify it. Many 
cases of untreated estivo- autumnal malaria present the same 
symptomatology, at least in part, as typhoid, and without an 
examination of the blood it is difficult to arrive at a diagnosis. 
The mistake of considering a typhoid infection as one of ma- 
laria, after quinine has been administered for over eight days 
without result, is, it seems to me, inexcusable, for all experience 
has shown that there is no malarial fever that will resist the 
action of quinine even after six days of its use; and yet hun- 
dreds of cases of typhoid fever are drenched with quinine, in 
supposedly malarial regions, under the mistaken notion that the 
estivo - autumnal fevers are so resistant to the drug that weeks 
of treatment are necessary. I have never seen a case of estivo- 
autumnal malaria which resisted the action of quinine for over 
six days, and doubt if any such exist, provided the quinine be 
properly administered. 

The mistake of confusing an estivo -autumnal infection with 
one of typhoid is rather rare. In such cases the malarial attack 
may last for weeks and end in spontaneous recovery or death. 

In differentiating these two diseases the microscopical exam- 
ination of the blood, the Widal test, and the therapeutic test by 
quinine are to be relied upon. If the parasites are present in 
the blood and the Widal test is negative, the diagnosis is at once 
demonstrated, although rare instances occur in which the Widal 
test is not obtained in typhoid; they are so rare, however, as to 
be of no diagnostic importance. If a blood examination is im- 
possible the use of quinine is indicated as a diagnostic measure. 
Any uncomplicated case of continued fever which resists the 
action of quinine properly given for a longer period than six 
days is not of malarial origin. 

While the quinine test is valuable, it should be remembered 
that the microscopic examination of the blood is greatly to be 
preferred. 

During the defervescence of the fever in typhoid, the tern- 



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TUBERCULOSIS 191 

perature may become intermittent, the curve much resembling 
that of a quotidian estivo- autumnal infection (Chart No. 19). 
Chills may also occur at this time, due to some septic compli- 
cation, thus further increasing the resemblance, and a diagnosis 
is made of typho- malarial fever. Such a diagnosis, without a 
blood examination, is utterly worthless, for unless the parasites 
of malaria can be demonstrated, we are justified in doubting the 
diagnosis. 

Tuberculosis . — Many cases of tuberculosis exhibit a tempera- 
ture chart closely resembling that of a quotidian estivo -autumnal 
infection; but while there may be chills there is no enlargement 
of the spleen, and examination of the chest will reveal pul- 
monary lesions not found in malaria. The examination of the 
blood for the malarial parasites, and of the sputum for the 
tubercle bacillus, will definitely settle the diagnosis. Not very 
rarely cases of tuberculosis are observed, complicated by estivo- 
autumnal fever, especially in the tropics, and here again the 
microscope is our only aid in making the diagnosis. Such cases 
are often stumbled upon accidentally while examining the blood 
of the patients for leucocytosis. (Chart No. 20.) 

Hepatic Abscess. — Certain eases of hepatic abscess show an 
intermittent temperature closely resembling that of estivo- 
autumnal malaria, and chills are apt to occur. The chief differ- 
ential clinical points are: In hepatic abscess the liver is enlarged 
and the spleen is not, as a rule; perspiration is more profuse, 
and a history of dysentery is obtainable. The examination of 
the blood will decide, as in malaria the parasites will be 
present, and the leucocytes decreased, while in hepatic abscess 
there are no parasites, and there is generally a marked leuco- 
cytosis. 

Ulcerative Endocarditis. — Certain cases of ulcerative endocar- 
ditis resemble quotidian estivo -autumnal fever, in that there are 
daily rises of temperature, accompanied by chills and sweating. 
(Chart No. 21.) Examination of the heart will generally suffice 
to determine the nature of such cases, and if not, an examina- 
tion of the blood will decide the question. 

Yellow Fever. — In regions infested with yellow fever certain 
pernicious cases of estivo -autumnal malaria are often mistaken 
for it. This is especially true of the so-called bilious remittent 
and hemorrhagic forms of pernicious malaria, in which the 
yellow tint of the skin, the congested eyes, the severe vomiting, 



192 ESTIVO- AUTUMNAL MALARIA 

the high temperature, and the occurrence of albumin in the urine, 
form a clinical picture closely resembling that of yellow fever. 
In such cases the examination of the blood is most important, 
and without it the diagnosis of yellow fever is always open to 
doubt. 

Pneumonia, Weil's disease, cholelithiasis, acute suppurative 
processes in the kidneys, liver, etc., have all been mistaken for 
attacks of the estivo- autumnal fever. 

Differential Diagnosis of the Pernicious Forms of 
Estivo -autumnal Fever.— In the various pernicious forms of 
the estivo -autumnal fevers examination of the blood is the one 
and only method of diagnosis which should be utilized. In these 
cases we cannot wait for the result of the quinine test> neither 
can we trust in the clinical symptoms present, for there are 
numerous other disease processes which so closely resemble in 
their symptomatology certaki forms of pernicious malaria, as to 
be almost indistinguishable from them. I shall mention the 
most important: 

Cerebral Apoplexy. — The differential diagnosis between cere- 
bral apoplexy and the comatose form of pernicious malaria is 
often extremely difficult. These cases are accompanied by coma, 
sterterous breathing, loss of the reflexes, etc., and often simulate 
cerebral apoplexy very markedly. The main points to be relied 
upon in arriving at a diagnosis are the high fever, although this 
is by no means constant, the age of the patient, and the splenic 
enlargement. An examination of the blood will generally decide 
the question at once. 

Meningitis, bulbar paralysis, acute mania, and tetanus, all of 
which resemble, in rare instances, certain forms of pernicious 
malaria, may all be differentiated by a microscopical examination 
of the blood. 

Sunstroke. — In the tropics, and especially among soldiers upon 
the march, sunstroke closely resembles certain forms of perni- 
cious malaria. It is a well-known fact that in the tropics the 
heat of the sun seems to excite grave malarial attacks, and this 
fact should ever be borne in mind in treating cases of so-called 
sunstroke in these latitudes. The history of previous attacks of 
malaria, the lack of anemia, the absence of splenic enlargement, 
and the abrupt onset of the symptoms will aid us in arriving at 
a diagnosis of sunstroke. In all such cases, however, an exam- 
ination of the blood should be made, and, if the estivo - autumnal 



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parasites be found, prompt and energetic treatment with quinine 
should be instituted. 

Among the other disease processes with which pernicious estivo- 
autumnal malaria may be confounded may be mentioned cholera, 
in which the diagnosis rests entirely upon the results of a blood 
examination ; dysentery, in which the diagnosis between true 
dysentery and the dysenteric form of pernicious malaria must be 
made, and which can only be done by the microscope; uremia, 
leukemia, pneumonia purpura hemorrhagica, and certain nervous 
diseases, such as hemiplegia, multiple neuritis, etc. 

The diagnosis of the complications attendant upon the estivo- 
autumnal malarial fevers will not be discussed. In conclusion, the 
examination of the blood has greatly simplified the diagnosis of 
the malarial fevers, and it can truly be said that he who to-day 
loses a patient from malarial fever because of inability to recog- 
nize the disease bears upon his shoulders a heavy weight of 
responsibility, which no regret will lessen. 

THE PROGNOSIS OF THE ESTIVO- AUTUMNAL MALARIAL FEVEKS 

In considering this portion of our subject, I shall discuss the 
prognosis in each form of estivo- autumnal fever separately, as 
by so doing we can arrive at a more just conception of the prog- 
nosis as it is affected by the occurrence of certain symptoms. 

The Quotidian Estivo -autumnal Fever. — The prognosis 
in cases of quotidian estivo -autumnal fever, provided they are 
not pernicious in character, and treatment is begun promptly, is 
always favorable so far as immediate danger to life is concerned. 
If, however, treatment is not persisted in for several weeks after 
the symptoms have disappeared relapses almost invariably occur, 
producing marked anemia and debility, and in such cases the 
prognosis should be more guarded. Several times I have ob- 
served fatal cases of anemia following attacks of this form of 
malarial fever. In one case the red cells fell to 400,000 per 
cubic millimeter before death. 

In cases which are unrecognized or improperly treated the 
prognosis is grave. Eepeated relapses, together with the com- 
plications which may arise, render a favorable prognosis impossible. 
When complications, such as pneumonia, nephritis, dysentery, etc., 
accompany the paroxysms, the prognosis is grave, and should be 
very guarded. 



TERTIAN ESTIVO -AUTUMNAL FEVER 195 

In all the quotidian cases the prognosis given should be in- 
fluenced by the fact that pernicious symptoms are apt to develop 
at any time. 

The Tertian Estivo- autumnal Fever. — In uncomplicated 
cases of tertian estivo -autumnal malaria, properly treated, the 
prognosis is good. If, however, the patient has suffered from 
previous attacks, and is greatly debilitated by them, the prog- 
nosis is much more grave, as such infections are very often 
resistant to treatment. This is probably due to diminished ab- 
sorption of the drug. In cases in which grave complications, 
such as nephritis and cardiac disease are present, the prognosis 
should be guarded, and often depends quite largely upon the 
nature and severity of the complication. The prognosis in the 
tertian variety of estivo -autumnal malaria is, I believe, better 
than that of the quotidian form. This I believe because of 
personal experience, although the Italian observers, from their 
experience in Italy, claim that the reverse is true. 

In untreated eases the prognosis is grave, and the liability 
of this form to develop pernicious symptoms should always be 
considered in making a prognosis. 

The Pernicious Forms of Estivo -autumnal Fever. — Per- 
nicious attacks of estivo -autumnal fever may be due to either 
the quotidian or tertian forms of the parasite, and the prognosis 
is the same in either case. 

The prognosis in the pernicious forms varies with the num- 
ber of paroxysms and the clinical variety of the fever. If the 
patient is first seen after having suffered from one or more 
pernicious paroxysms, the prognosis is very grave, although, if 
treatment be rigorously instituted, not hopeless. If seen during 
the first paroxysm the prognosis is grave, and treatment should 
be at once instituted. In these cases a fatal paroxysm may fol- 
low, even after the most energetic treatment. 

The Cerebral Pernicious Forms. — The prognosis is most grave 
in those forms of pernicious malaria which exhibit cerebral 
symptoms. This is especially true of the comatose form, in 
which the prognosis is always very grave. A large number of 
such cases recover with proper treatment, but this form furnishes 
the greater part of the cases of fatal malarial fever. Untreated, 
the cerebral forms of pernicious malaria are almost invariably 
fatal. 

The Algid Form. — The prognosis in the algid form is almost 



196 ESTIVO- AUTUMNAL MALARIA 

as grave as it is in the cerebral forms, and such cases, if un- 
treated, are generally fatal. Prompt treatment will save many, 
but not a few go on to a fatal termination despite all treatment. 

The Choleraic Form. — The prognosis in this form is also very 
grave, and Marchiafava and Bignami believe that it ranks next 
to the cerebral forms in fatality. 

The Dysenteric Form. — The prognosis in the dysenteric form 
of estivo- autumnal fever is grave, and I have observed several 
cases which resulted fatally in spite of treatment. The prog- 
nosis in such cases should depend quite largely upon the severity 
of the dysenteric symptoms, and the degree of anemia present. 
The paroxysms are apt to be hidden by the intestinal phenomena, 
and the malarial element remains long undetected before proper 
treatment is begun. Death is generally the result of exhaustion 
and anemia in these cases. 

The Pneumonic Form. — In the pneumonic form the prognosis 
is grave, and, if untreated, a large proportion of the cases result 
fatally. 

The prognosis in the other forms of pernicious malarial fever, 
as the diaphoretic, cardialgic, and hemorrhagic, is always grave. 

Irregular and Continued Fevers.— The prognosis in these 
cases is more grave than in the regularly intermittent estivo - 
autumnal attacks, but less so than in the pernicious forms. 

General Factors Influencing Prognosis. — There are some 
general factors to be taken into account in making a prognosis 
in the estivo -autumnal malarial fevers, the chief of which are: 
location, race, age, occupation, and physical condition of the 
patient. 

1. Location. — In certain localities the prognosis is much more 
grave than in others. In the tropics the prognosis in this class 
of malarial fevers is much more grave than in temperate regions; 
and again, in certain regions in the tropics these fevers are much 
more fatal than in others. For instance, estivo -autumnal mala- 
ria is more serious and fatal in Santiago, Cuba, than in Havana, 
Cuba. 

2. Race. — The negro enjoys a relative immunity from the 
estivo -autumnal fevers, and the prognosis is more favorable than 
in the lighter -skinned races. Koch has conclusively proven that 
such is the fact. ■ 

3. Age. — The prognosis is most grave at the extremes of life. 
In the aged it is always very grave. 



PROGNOSIS OF SEQUELS 197 

4. Occupation and Position in Life. — The prognosis in those 
well-to-do is almost always more favorable than in the poor. 
This is so, both because the physical condition of the first class 
is generally better than that of the second, and that, in the first, 
the disease is at once treated, while in the second it often exists 
for some time before relief is sought. 

The prognosis in the case of soldiers serving in tropical cli- 
mates is always grave, as has been conclusively proven in the 
case of our soldiers in Cuba and the Philippine Islands. While 
intelligent treatment has, in the vast majority of cases, pre- 
vented a fatal termination of the acute attack, the debility and 
anemia occasioned by them have too often proved fatal. 

5. Physical Condition. — It is obvious that the prognosis is 
more grave in the cases of individuals in ill health than in those 
who have been healthy previous to the malarial attack. 

Prognosis in Complications. — The prognosis in cases of 
estivo- autumnal malaria attended by complications, is that of the 
fever and the added complication. It is always more grave than 
in uncomplicated cases. Among the complications which render 
very grave the prognosis are tuberculosis, pneumonia, the infec- 
tious fevers, and sunstroke. 

Prognosis of Sequels. — As a general rule it may be said 
that the prognosis of the sequelae of estivo -autumnal malaria is 
good, though recovery may be long delayed. The most import- 
ant of the sequelae will be considered in detail. 

Nervous and Mental Sequela}. — The prognosis in the various 
nervous and mental sequelae is good, and recovery usually occurs 
within a few weeks or months. Insanity, occurring as a sequelae 
of malaria, does not generally persist for more than six months, 
although there may be impairment of the mental faculties for a 
long time afterward. Malarial paralyses possess a good prog- 
nosis, recovery usually occurring. 

Nephritis. — The majority of nephrites occurring with, or fol- 
lowing these fevers, are rapidly recovered from, and the prog- 
nosis is good. A few cases become chronic, and in rare instances 
the acute form may terminate fatally. 

Post -malarial Anemia. — The prognosis in anemia following 
these fevers depends entirely upon the character of the anemia. 
I have already described the forms of anemia occurring after 
these fevers and will not reconsider them here. Suffice it to say, 
that the prognosis in the simple secondary anemia is generally 



198 ESTIVO - AUTUMNAL MALARIA 

good, the blood regaining its normal number of red cells after 
weeks or months. This may be the result in cases in which the 
red cells have been very markedly reduced in number. As a rule, 
in these cases, the red cells increase rapidly until they number 
about 2,500,000 per cubic millimeter, after which the increase is 
very slow. 

The prognosis in those cases in which the anemia assumes a 
pernicious type is always most grave, death usually occurring. 

Malarial Cachexia. — In cases in which a change of locality 
can be effected the prognosis, under suitable treatment, is good, 
otherwise it is grave. 

The following axiom should never be forgotten: The prog- 
nosis in all cases of estivo- autumnal malaria is grave, because 
at any time during their course pernicious symptoms may de- 
velop. 

While it is comparatively easy to give a prognosis in these 
fevers of malaria so far as immediate recovery from an attack 
is concerned, the prognosis as to ultimate cure of the malarial 
infection should be very guarded. Relapses are sure to occur 
unless quinine is given for months after the first paroxysm, and 
very often a change of climate is found absolutely necessary. 
One of the most discouraging features of the estivo -autumnal 
variety of malaria is the extreme tenacity of the infection. 



CHAPTER XVIII 

THE PROPHYLAXIS AND TREATMENT OF THE ESTIVO- AUTUMNAL 
FEVERS 

PKOPHYLAXIS 

The subject of prophylaxis in the estivo- autumnal fevers is 
of very great importance, and in the light of our recently gained 
knowledge of the transmission of the disease by the mosquito, 
one which should receive the attention of every physician and 
sanitarian. Until recently we were ignorant of the source of 
the malarial poison, and could do but little toward preventing 
its spread; but now it is not too much to hope that in time the 
malarial fevers will be as rare as are now some of the acute 
infectious diseases. Prophylactic measures may be divided into 
general and personal, and these will be considered separately. 

General Prophylactic Measures. — We now know that the 
mosquito not only transmits the disease to man, but acts as an 
intermediary host of the parasite; it follows, then, that in order 
to prevent malarial disease the most important general measure 
is the destruction of the mosquitoes and their larvae. Many 
methods have been devised for the latter purpose. We are in- 
debted to L. 0. Howard for the most valuable of these, and I 
shall quote largely from his most valuable study* in the con- 
sideration of this portion of our subject. 

Regarding the destruction of the larvae of the mosquito and 
the abolition of its breeding places he says: 

"Altogether the most satisfactory ways of fighting mosquitoes 
are those which result in the destruction of the larvae or the 
abolition of their breeding places. In not every locality are 
these measures feasible, but in many places there is absolutely 
no necessity for the mosquito annoyance. The three main pre- 
ventive measures are the draining of breeding places, the intro- 
duction of small fish into Ashless breeding places, and the treat- 
ment of such pools with kerosene. These are three alternatives, 

*«The Mosquitoes of the United States," Bull. 25, Dept. of Agriculture. 
(199) 



200 ESTIVO- AUTUMNAL MALARIA 

any one of which will be efficacious, and any one of which may 
be used where there are reasons against the trial of the others. 

"Kerosene on Breeding Pools. — In 1892 the writer published 
the first account of extensive out-of-doors experiments to deter- 
mine the actual effect upon the mosquitoes of a thin layer of 
kerosene upon the surface of water in breeding pools and the 
relative amount to be used. He showed the quantity of kerosene 
necessary for a given water surface, and demonstrated further 
that not only are the larvse and pupae thereby destroyed almost 
immediately, but that the female mosquitoes are not deterred 
from attempting to oviposit upon the surface of the water, and 
that they are thus destroyed in large numbers before their eggs 
are laid. He also showed approximately the length of time for 
which one such treatment would remain operative. 

"The quantity of kerosene to be practically used, as shown 
by the writer's experiments, is approximately one ounce to fifteen 
square feet of water surface, and ordinarily the application need 
not be renewed for one month. Since 1892 several demonstra- 
tions, on both a large and a small scale, have been made. Two 
localities were rid of the mosquito plague under the supervision 
of the writer by the use of kerosene alone. On ponds of any 
size the quickest and most perfect method of forming a film 
of kerosene will be to spray the oil over the surface of the 
water. 

"Drainage. — The remedy which depends upon draining breed- 
ing places needs no extended discussion. Naturally the draining 
off of the water of pools will prevent mosquitoes from breeding 
there, and the possibility of such draining and the means by 
which it may be done will vary with each individual case. The 
writer is informed that an elaborate bit of work which has been 
done at Virginia Beach bears on this method. Behind the hotels 
at this place, the hotels themselves fronting upon the beach, was 
a large fresh -water lake, which, with its adjoining swamps, was 
a source of mosquito supply, and it was further feared that it 
made the neighborhood malarious. Two canals were cut from 
the lake to the ocean, and by means of machinery the water of 
the lake was changed from a body of fresh to a body of salt 
water. Water that is somewhat brackish will support mosquitoes, 
but water which is purely salt will destroy them. 

"Practical Use of Fish. — The introduction of fish into Ashless 
breeding places is another matter. It may be undesirable to 



FISH AND MOSQUITOES 201 

treat certain breeding places with kerosene, as, for instance, 
water which is intended for drinking, although this has been 
done without harm in tanks where, as is customary, the drinking 
supply is drawn from the bottom of the tank. An interesting 
case, noted in "Insect Life" (Vol. IV, p. 223), in which a pair of 
carp was placed in each of several tanks in the Riviera, is a 
case in point. The value of most small fishes for the purpose of 
destroying mosquito larvas was well indicated by an experience 
described to us by Mr. C. H. Russell, of Bridgeport, Connecticut. 
In this case a very high tide broke away a dike and flooded the 
salt meadows of Stratford, a small town a few miles from Bridge- 
port. The receding tide left two small lakes, nearly side by side 
and of the same size. In one lake the tide left a dozen or more 
small fishes, while the other was Ashless. An examination by 
Mr. Russell in the summer of 1891 showed that while the fishless 
lake contained tens of thousands of mosquito larvae, that con- 
taining the fish had no larva?. 

"The use of carp for this purpose has been mentioned in the 
preceding paragraph, but most small fish will answer as well. 
The writer knows of none that will be better than either of the 
common little sticklebacks (Gasterosteus aculeatus or Pt/gosteus 
pungitius). They are small, but very active and very voracious. 

"During the past few years kerosene has been rather exten- 
sively used at many places in an effort to limit the mosquito 
supply. As already pointed out, there are many places where the 
source of mosquito supply is definitely limited and easy of treat- 
ment, and in such cases, on account of the cheapness of kerosene, 
it will be the best means of eradication. In other places where 
communities are surrounded with swamp land, or in the case of 
extensive sea marshes, kerosene can be practically used in con- 
nection with other and more elaborate measures, comprehending, 
as a rule, dyking and draining." 

Celli and Cassigrandi* have investigated very thoroughly the 
action of various agents upon the mosquito, and their conclu- 
sions are as follows: 

" (1) Of the whole period of the cycle of development of mos- 
quitoes the stages in which they are most easily destroyed are 
those of larvas and of the aerial mosquito, and larvas are most 
easily killed the younger they are. 

"(2) To kill the larvae, among numerous substances experi- 

*"Annali d'lgiene Sperimentale," Vol. IX, Fase. Ill, 1899. 



202 ESTIVO- AUTUMNAL MALARIA 

mented with, these will have, in decreasing order, culicidal action: 
(a) Mineral: sulphurous oxide, permanganate of potash with 
hydrochloric acid, common salt, potash, ammonia, carburet of 
lime, corrosive sublimate, chloride of lime, the bisulphites, sul- 
phate of iron or copper, lime, bichromate of potash, and sodium 
sulphite. (&) Organic: powders of the unexpanded flowers of 
chrysanthemum, tobacco, petroleum and oils, formalin, cresol, 
certain aniline colors (gallot, green malachite), coal tar. Taking 
into account, however, the dose necessary to kill the larvae, the 
practicability and the price, all of the mineral and some of the 
organic substances are excluded, and there remain as available 
the vegetable powders, petroleum, and the aniline colors. 

" (3) To kill aerial mosquitoes, we have odors, fumes, or gases. 
Among the odors are turpentine, iodoform, menthol, nutmeg, cam- 
phor, garlic. Among the fumes are tobacco, chrysanthemum 
powder, fresh leaves of eucalyptus, quassia wood, pyrethrum 
powder. Among the gases, sulphuric oxide. It is, however, to 
be noted that for these odors, fumes, or gases to exercise their 
culicidal action they must fill or saturate the whole ambient; 
otherwise they produce only apparent death, or at most only a 
culicifugal action, which sometimes in houses may be useful in 
protecting man from being bitten by mosquitoes, and preventing 
the latter infecting him when they have sucked the blood of 
malarious persons. 

" (4) The problem of the destruction of mosquitoes is experi- 
mentally soluble, but practically it will only be so when economic 
interests desire it. In this latter sense it is remarkable that the 
old larvicidal use of petroleum has not become much diffused in 
those places where it is very cheap. The chrysanthemum plants 
might be grown on a large scale, this making the malarial place 
itself produce that substance which frees it of the mosquitoes 
that infest it. 

" (5) The opportune season for killing the larvaa is in the 
winter, when they are in least numbers in the waters and new 
generations are not born; this also is the season for their 
destruction in houses, for they come here for a warmer abode. 
Their habits and places of nesting should be studied to this end. 
This may not be accomplished on a large scale as easily as some 
boast; nevertheless, after the treasures spent by nations and indi- 
viduals for preserving vines and vegetation from the oidium, the 
peronospora, and the phylloxera, we may hope that something 



PEE SON AL PROPHYLAXIS 203 

may be done for protecting the life of man from the mosquitoes 
of malaria." 

It would seem from the quotations cited that next to abol- 
ishing the breeding places of the mosquitoes the use of kerosene 
is at once the cheapest and most practicable agent of which we 
have knowledge, at present, for the destruction of the larvae of 
the insect. If all stagnant pools and ditches surrounding dwell- 
ing-houses in malarious localities were treated once a month with 
kerosene as recommended by Howard, malarial fever in such 
localities would be very greatly diminished and perhaps even 
disappear. 

The planting of eucalyptus trees has been urged by numerous 
observers as a protection against malaria, and while there seems 
to be some truth in the theory, it has been shown by Nuttall 
that it is not always successful. 

Personal Prophylaxis. — A great deal may be done in the 
way of personal prophylaxis against malaria by the adoption of 
certain well-known measures. 

If one is obliged to travel in malarious districts, the season of 
the year in which the malarial fevers are least prevalent should 
be selected. The use of a mosquito net is most important. It 
should be the constant companion of the traveler in the tropics, 
and every night should be passed beneath it. The adoption of 
the mosquito net by armies operating in malarious regions, espe- 
cially in the tropics, would undoubtedly do more toward prevent- 
ing malarial disease than any other sanitary measure. Since the 
adoption of the mosquito net in the barracks of the United States 
troops at Camp Columbia, Havana, Cuba, malarial fever has 
become very rare, whereas it was very common. 

In selecting camping sites, or locations for buildings in ma- 
larious regions, high, well -drained land should be chosen, and 
exposure at night, unless protected by the mosquito netting, 
should be avoided. 

Drinking water should always be boiled, for though malaria is 
but seldom conveyed by it, and then only accidentally, the measure 
may prevent other diseases which would so deplete the organism as 
to render it very easily susceptible to the malarial poison. It is 
advisable to sleep above the ground floor if mosquitoes are numer- 
ous, and to have the windows protected by screens and netting. 
For the protection of the hands and face during the day, or when 
compelled to travel at night, and mosquito nets cannot be used, 



204 ESTIVO- AUTUMNAL MALARIA 

various odorous substances have been successfully used. These 
are all smeared upon the skin and renewed as needed. Among the 
most useful are : oil of pennyroyal, camphor, kerosene, oil of 
eucalyptus, a mixture of oil of tar and sweet oil, as recommended 
by Nuttall, oil of anise and tar water; the last, which is advocated 
by Osborne, and quoted by Nuttall, is prepared as follows: "Coal 
tar is placed in a shallow vessel, and oil of tar or oil of turpentine 
is added to it and stirred. The vessel is then filled with water 
and allowed to stand some days until the water is impregnated. 
The water is used as a wash." 

For the protection of houses from mosquitoes the windows 
should be well screened by fine netting, and kept closed, unless 
screened, at night. The burning of pyre thrum powders within 
the house is efficacious. 

It is a fact well sustained by practical experience that a most 
valuable aid in the prophylaxis of malaria, in malarious regions, 
especially in the tropics, is the daily exhibition of a small dose of 
quinine, preferably the sulphate, in doses of .10 to .20. 

TREATMENT OF THE ESTIVO -AUTUMNAL MALARIAL FEVERS 

The treatment of the estivo- autumnal malarial fevers may be 
divided into hygienic and medicinal, and both should be combined 
in every case. 

Hygienic Treatment. — Rest is most important, and every case 
of estivo -autumnal malaria should be confined to bed, so long as 
there are active symptoms present. While many cases recover 
without being thus confined, and some without any treatment, it is 
a good general rule to insist upon absolute rest in these cases. 
Treatment by quinine is always much more effective if the patient 
keeps his bed, and recovery is always more rapid and complete. 
The danger of pernicious symptoms developing in these cases 
should never be forgotten and should always be guarded against. 

Diet. — In all cases the diet should be light during the par- 
oxysms, consisting of milk, soups, soft-boiled eggs, etc. After 
the acute symptoms are passed a more liberal diet is indicated, 
and the more nutritious it is the better, as in these cases the 
debility and anemia which often follow fever is astonishing. 
The diet should be regulated in accordance with the symptoms 
present. 

The sick room should be, if possible, in an upper story, and 



MEDICINAL TREATMENT 205 

well ventilated. The windows should be screened, and every pre- 
caution taken to avoid cold drafts. 

The patient should be guarded against any irritation, as in 
many cases of estivo- autumnal malaria the nervous irritability 
is very great. 

A change of climate in cases which have suffered from re- 
lapses is often advisable and necessary, and without such a 
change treatment may be of but little avail. 

Medicinal Treatment. — The medicinal treatment of the 
estivo -autumnal malarial fevers may be summed up, in the over- 
whelming majority of cases, in the one word "quinine." In qui- 
nine we possess a true specific for all forms of malaria, and dis- 
appointment and disgust will follow the use of other drugs, 
which are from time to time vaunted as equal or superior to 
quinine. As is well known, cinchona was introduced into Eu- 
rope in 1640, and immediately gained a well-deserved repute in 
the treatment of fevers of malarial origin. Its active principle, 
an alkaloid, is the quinine of to-day, and various salts of the 
drug are now available. In considering the therapeutic use of 
quinine or its salts in the estivo -autumnal malarial fevers, the 
following points should receive our attention: 

1. The Action of Quinine upon the Estivo -autumnal Parasite. 

2. The Time of Administration. 

3. The Form in which it should be Administered. 

4. The Methods of Administration. 

5. The Amount to be Administered. 

6. Contra -indications to its Administration. 

1. The Action of Quinine upon the Malarial Parasites. 
— The beneficial action which quinine exerts upon the malarial 
fevers is due to the fact that it is a protoplasmic poison, acting 
directly upon the malarial parasites. Binz, in 1867, was the 
first observer to enunciate this theory of the action of quinine, 
and Golgi, Antolisei, Romanowsky, Mannaberg, Dock, Marchia- 
fava, Celli, Sternberg, and others have proven its truth. All 
these observers have shown that quinine causes the degeneration 
of the young malarial parasites, most marked at the time of 
segmentation. Marchiafava and Bignami have carefully studied 
the effects of quinine upon, the estivo -autumnal parasites, and 
conclude their observations as follows: "Quinine acts upon the 
malarial parasites in that phase of their life in which they are 
nourished and developed. When the nutritive activities cease, 



206 ESTIVO- AUTUMNAL MALARIA 

by an arrest of the transformation of hemoglobin into black 
pigment, and the reproductive phase begins, the quinine is in- 
effectual in its action.' 7 

From personal observations I have noted the following 
changes in the estivo- autumnal parasites; these changes are 
confined entirely to the young hyalin and pigmented intracor- 
puscular forms: 

A few hours after the administration of quinine the small 
hyalin parasites, both quotidian and tertian, have lost their 
amoeboid motion, and appear more or less contracted or distorted 
in shape. The perfect "ring-form' 7 is lost, and bizarre shapes are 
common. The red cell containing the parasite is generally green 
in color and is very apt to be much crenated. The young pig- 
mented forms appear shrunken, and their protoplasm more gran- 
ular, while the infected red cell is very dark green in color, 
shrunken, and crenated. 

A study of the staining reactions of the malarial parasites 
after they have been acted upon by quinine reveals the reason for 
the morphological changes noted to consist in the degeneration of 
the vital elements of the organism, brought about by the drug. 
Komanowsky* has devoted much study to this subject, and has 
demonstrated that after quinine has been administered the para- 
sites lose their affinity for various stains, this loss being confined 
almost entirely to the chromatin substance of the nucleus, and 
that most of the newly formed segments are without a nucleus. 

2. Time of Administration. — From what has been said it will 
be seen that quinine is most efficacious if it be present in the 
blood when segmentation of the parasites occurs, as it acts most 
energetically upon the newly born parasites. In the regularly 
intermittent tertian and quartan fevers, as well as in the uncom- 
plicated quotidian and tertian estivo -autumnal fevers, the time of 
administration can be so arranged as to accomplish this result, 
but in the pernicious and irregular forms of estivo -autumnal 
malaria this is impossible. 

In the regular quotidian and tertian estivo -autumnal fevers the 
quinine should be administered in doses of 1.5 to 2, or grs. xx 
to xxx, four to six hours before the expected paroxysm, or the 
latter portion of the previous attack. 

In pernicious and irregular cases this rule cannot be applied; 
in the pernicious eases the administration of quinine is indicated 

*Cent. fur Bak't., 1892, XI., No. 6, 7. 



TIME OF ADMINISTRATION OF QUININE 207 

at once, while in the irregular cases a dose of .40 should be given 
every four hours for several days. The administration of .35 to 
.40, or grs. v to vi, of quinine, every four hours, I have found to 
be fully as satisfactory in the treatment of even the regularly 
intermittent estivo- autumnal fevers, as the single large dose first 
mentioned, and the interrupted method of administration is the 
one which I personally prefer. The results obtained are as good, 
and the discomfort to the patient is, as a rule, much less. Dock,* 
in a most valuable paper, concludes in favor of the administration 
of large doses, three to six hours before the expected paroxysm. 
Theoretically, this is absolutely correct, and should always be fol- 
lowed in the regularly intermittent malarial fevers of benign ter- 
tian and quartan causation; but in the estivo -autumnal fevers the 
results obtained are no better, in my experience, than those in 
which the numerous smaller doses have been given. It should 
also be remembered that many patients are unable to absorb but a 
small quantity of quinine at a time, and in such cases the greater 
part of a large dose would be simply wasted. I am convinced that 
many of the most resistant cases of estivo -autumnal malaria 
depend upon the inability of the patient to absorb the quinine 
which is administered. There are certain cases, however, which 
do not respond to small doses of quinine, often repeated, but 
which recover rapidly under large doses. 

As in the treatment of all diseases, each case should be judged 
individually, and treated accordingly. 

In all cases which exhibit pernicious symptoms, the quinine 
should be administered at once. 

3. The Form of Quinine to be Administered. — There are 
ten salts of quinine which are, or have been used, in the treat- 
ment of estivo -autumnal malaria, but of these there are but 
two which merit general use. These are the sulphate and the 
dihydrochlorate or bimuriate of quinine. The sulphate contains 
74.31 per cent of quinine, while the bimuriate contains 81.61 
per cent. The first is soluble in the proportion of one part to 
nine parts of water, while the latter is soluble in the proportion 
of one part to .96 parts of water. 

From this it will be seen that the bimuriate of quinine is to 
be preferred theoretically, but practically, on account of its 
cheapness, the sulphate is most useful. 

In cases in which the hypodermic or intravenous use of the 

*" Quinine in Malaria," Jour. Am. Med. Association, July 29, 1899. 



208 ESTIVO- AUTUMNAL MALARIA 

drug is indicated, the hydrochlorate (the bimuriate) should al- 
ways be used. 

4. Methods op Administration op Quinine. — Quinine may 
be administered in three ways, i. e., by the mouth, hypoder- 
mically, and intravenously. In rare instances it has been ad- 
ministered by the rectum, but this method is undeserving of 
consideration, as it is unsatisfactory and unnecessary. 

Administration by the Mouth. — In the great majority of cases 
quinine is administered by the mouth. The form of salt used 
is generally the sulphate, in the form of solutions, capsules, 
pills, or tablets. This method of administration is the most 
satisfactory in the great majority of cases, and, save in rare in- 
stances, can be resorted to. When possible, the quinine should 
be given in solution, a drop of dilute hydrochloric or sulphuric 
acid being added for every grain (.065) of the drug. To disguise 
the horribly bitter taste which the solution has, the syrup of yerba 
santa is most efficient. Many cases, however, refuse to take the 
quinine in solution, and in such instances capsules, pills, or tablets 
may be used. Of these the gelatin capsules are much to be pre- 
ferred, as they are quickly soluble. Tablets are generally to be 
preferred to pills, which are too often extremely insoluble. 

Personally I use quinine in solution or in capsules, in admin- 
istering the drug by the mouth. 

Administration by the Hypodermic Syringe. — In cases of estivo- 
autumnal malaria, in which the symptoms are of pernicious char- 
acter, and, again, in cases which cannot take quinine by the 
mouth, the hypodermic use of the drug is indicated. In perni- 
cious cases it should be resorted to without delay, as it is neces- 
sary to bring the drug in contact with the parasites as soon as 
possible. 

The solution which is generally used is the following: 

~&> Hydrochlorate of quinine 5. (grs. lxxv). 

Distilled water q. s. add 10. (z jiss). 

In this solution 1 e.c. (15m) contains .5 (grs. vjiss) of quinine. 

Extreme care should be used in making the injection, as in- 
duration and even abscess formation is apt to follow the admin- 
istration of the drug in this manner. The syringe should be 
sterilized thoroughly, and also the skin over the area in which 
the injection is to be made; the solution should be perfectly clear 



INTRAVENOUS INJECTION OF QUININE 209 

and freshly prepared; the abdomen, back, or gluteal region may 
be selected, but the gluteal region is preferable; the injection 
should be made into the muscles, therefore the needle of the 
syringe should be deeply inserted; the wound made by the needle 
should be covered with a thin coating of collodion. 

Much discomfort and pain generally follows the injection of 
quinine into the subcutaneous tissues, and if the operation is 
carelessly done, no precautions as to cleanliness being observed, 
severe necrosis of the skin and abscess -formation may occur. 
If aseptic precautions are observed, however, these may almost 
invariably be avoided, although more or less induration around 
the site of injection is of common occurrence. 

Intravenous Injection of Quinine. — To Baccelli we owe this 
method of administering quinine. It is indicated whenever the 
most prompt effect of the drug is required, as in pernicious 
cases after one paroxysm has been succeeded by another, or the 
patient's strength is rapidly failing, or when other treatment has 
proved unavailing. Marchiafava and Bignami urge this method, 
especially in the algid forms of pernicious estivo- autumnal fever. 

Baccelli's solution is as follows: 

J?, Hydroehlorate of quinine .... 1. (grs. xv) . 

Chloride of sodium 75 (grs. xji) . 

Distilled water q. s. add ..... 10. (z ijss). 

The whole amount is to be injected and the solution should be 
perfectly clear and tepid. 

The method of injecting is thus described by Baccelli*: "After 
the veins of the forearm have been made turgescent by means of 
a circular tourniquet, we introduce a Pravaz needle from below 
upward into the lumen of the vein. We select a small one, in 
order to avoid hemorrhage afterward. The syringe holds 5 cen- 
timeters and is filled according to the dose which is to be given, 
and connected with the needle before its introduction." 

It is, of course, very important that all the precautions as 
regards cleanliness should be observed here as in the hypodermic 
injection of the drug. 

5. The Amount of Quinine to be Administered. — There is 
no doubt but that we err more often upon the side of excess in 
administering quinine than vice versa. It is not uncommon to 

*"Za Riforma Mediea," January, 1890. 



210 ESTIVO- AUTUMNAL MALARIA 

observe the use of from 5 to 6 grams of the drug during the 
twenty -four hours, even in the mild intermittent fevers. Such 
large doses are simply criminal, for they occasion much harm to 
the system. From personal experience I believe that 2 grams, 
or 30 grains, of quinine in the twenty-four hours is amply suffi- 
cient to cure any case of ordinary estivo- autumnal malaria, if it 
is properly administered. I have never seen a case in which 
treatment was begun in time which did not succumb to that 
amount of the drug, and I have seen many cases recover rapidly 
when but 1.3 grams, or xx grains, were administered during the 
twenty-four hours. 

When the drug is used hypodermically a dose of .5 grams, 
or 7% grains, should be administered, and repeated, if necessary, 
until about 1.3 grams (grains xx) have been injected. Some 
very severe cases may require more than the above amount, but 
they will be rare, and will probably prove fatal in any event. 

When given intravenously the dose which Baccelli recommends 
is one gram. 

Stated briefly, the amount of quinine to be used in the treat- 
ment of estivo -autumnal malaria is as follows: By the mouth, 1.3 
to 2.5 grams (grains xx to xxxv) ; hypodermically, .65 to 
1.3 grams (grains x to xx) ; intravenously, 1 gram (grains 
xvi). 

As soon as the active symptoms of the paroxysm have sub- 
sided, the dose of the quinine which has proven efficacious may 
be gradually diminished, but the drug should be used for several 
weeks afterwards. 

An ordinary case of either quotidian or tertian estivo -autumnal 
malarial fever should be treated, then, as follows: The patient 
should, if possible, keep his bed. The bowels should be thor- 
oughly opened by calomel, .32 grams (grains v), and the diet 
should be light and nourishing. Quinine, .32 or grains v, should 
be given every four hours until after the active symptoms of the 
fever have disappeared, and every five hours for a period of 
three days following. For the next week quinine in doses of one 
gram (grains xvi), on every other day should be admin- 
istered, and for a period of at least three months afterwards, a 
dose of quinine of 1.3 grams (grains xx), should be taken 
every sixth day. If this treatment is followed out a cure of the 
disease will be reasonably sure. 

One of the most serious mistakes which is made in the treat- 



CONTRAINDICATIONS TO QUININE 211 

ment of estivo- autumnal malaria is the too early abandonment 
of quinine. These infections are very resistant, and relapses are 
almost sure to occur unless quinine is administered for weeks 
after the patient is apparently well. 

6. Contraindications to the Administration of Quinine.— 
There are certain individuals, few in number, who undoubtedly 
are unable to take quinine. In all, the use of large doses of this 
drug produce unpleasant symptoms, such as tinnitus aurium, 
vertigo, confusion of thought, etc., but in certain individuals 
symptoms occur which may even endanger life, or, at least cause 
such suffering as to render the administration of the drug inad- 
visable. Among such symptoms may be mentioned amaurosis, 
which may be persistent, deafness, dysponcea, cardiac weakness, 
severe cutaneous eruptions, metrorhagia, hemorrhage from the 
bowels, hematuria, and even fatal collapse. 

Patients who suffer from these unusual symptoms, which are 
really due to the poisonous effect of quinine, even in therapeutic 
doses, upon them, are generally aware of their idiosyncrasy in 
this respect and refuse to allow it to be given, and, indeed, the 
appearance of such symptoms are contraindications to the use of 
the drug. In such cases some substitute for quinine must be 
used, and the most important of these will now be considered, 
always remembering that there is no substitute for quinine when 
it can be borne. 

Substitutes for Quinine. —Among the alkaloids besides 
quinine which have been separated from the cinchona bark are 
quinidine, cinchonidin, and cinchonine, all of which have been 
used successfully in place of quinine. 

Euchinin. — This is a new tasteless product, an ethyl carbonate 
of quinine. It has many of the bad effects of quinine, as deaf- 
ness and derangement of vision, and it has to be given in larger 
doses. St. George Gray, Mori, Lewkowitz, and Goniev have used 
it in many cases of malarial fever, and claim that it is a valuable 
addition to our therapeutic resources. The dose is a little less 
than twice that of quinine. Personally I have had no experience 
with this drug. 

Methylene Blue. — The use of this drug in malarial fever was 
first advocated by Guttman and Ehrlich, whose attention was 
drawn to it by the observations of Celli and Guarnieri, that by its 
use the malarial parasite could be stained while living. In iso- 
lated cases it undoubtedly effects a cure, but it is much less 



212 ESTIVO- AUTUMNAL MALARIA 

effective than quinine. Marchiafava and Bignami think that it 
is worse than useless, as it may produce strangury, diarrhea, and 
temporary albuminuria. Thayer regards its use favorably, but 
has found that the malarial parasites acquire a seeming tolerance 
to it. From personal observations I am convinced that some- 
times it effects a cure, but that it is very much less valuable than 
quinine. The dose is from .5 grams (grains viii) to .1 gram 
(grains xvi) in the twenty -four hours. 

The urine is colored blue by it, and it is always well to warn 
the patient of this fact. 

Phenocoll. — The hydrochlorate of phenocoll, a derivative of 
phenacetin, has been investigated by numerous observers, notably 
Albertoni, Pucci, Novi, Anconi, and F. Plehn. The general con- 
sensus of opinion is that, while it is sometimes useful in the 
mild tertian and quartan fevers, it is of but little use in the 
treatment of the estivo- autumnal infections; while it is not free 
from injurious effects, as symptoms of collapse have followed its 
use. The dose is from 1 to 3 grams (grains xvi to lv) during 
the twenty -four hours. 

Lemons. — Tomassi-Crudelli has observed a marked improve- 
ment in old malarial infections from the use of lemon juice and 
decoction of the lemon. 

From this brief summary of the drugs which are used as 
substitutes for quinine, it will be observed that they are few in 
number, and that none of them can be ranked with quinine, which 
is the true specific for all malarial diseases. 

Treatment of Special Symptoms and Complications. — 
There can be no doubt that a cathartic dose of calomel enhances 
the effect of quinine, and it should always be used even in those 
eases presenting intestinal symptoms. 

The vomiting if exhausting may be controlled by hypodermic 
injections of morphine. 

The headache is best relieved by cold applications, and if 
there is great nervous excitement or delirium, morphine is indi- 
cated. The symptoms occurring during pernicious attacks should 
receive proper treatment. High temperature, if it shows no signs 
of declining, should be treated with tepid baths; cardiac weakness, 
by suitable stimulants ; algid symptoms should be treated by 
stimulants, massage, and heat applied by means of hot-water 
bottles and warmed blankets ; collapse should be treated by hypo- 
dermic injections of brandy, strychnine, ether, and by transfusion. 



TREATMENT OF CONVALESCENCE 213 

Complications. — The complications should be appropriately- 
treated, the malarial infection being promptly conquered by 
quinine. 

Treatment During Convalescence. — During convalescence, 
besides the administration of quinine in the manner indicated, 
the use of some form of iron is advisable, on account of the 
marked anemia which is usually present. Bland's pill is a very 
valuable therapeutic aid in these cases. In cases which show a 
profound degree of anemia, and which do not improve with iron 
alone, arsenic should be given in the form of Fowler's solution, 
and administered in gradually increasing doses. 

The diet should be generous and nutritious, sufficient outdoor 
exercise should be insisted upon, and precautions taken to avoid 
reinfection. 

In all cases where it is possible, a change of climate to a 
high, dry altitude, known to be non- malarious, should be urged. 
This will do more for the patient than any other therapeutic 
measure. Bitter tonics are often very useful, and the use of 
some good mineral water is indicated. 

The above remarks apply as well in the treatment of chronic 
malaria cachexia as in convalescence from acute attacks. 

The treatment of the* fcequehe of the estivo- autumnal malarial 
fevers will not be considered here, as it differs in no way from 
that ordinarily pursued in the diseases themselves, save that the 
malarial element should always be remembered and acute attacks 
guarded against. 



INDEX 



Abscess, hepatic, diagnosis from, 191. 
Age, as predisposing cause of, 61. 

in prognosis, 196. 
Air, direct infection by, 62. 
Albuminuria, as a sequela of, 88, 179. 
Algid form, prognosis of, 195. 

symptoms of, 152. 
Altitude, as predisposing cause, 59. 
Amaurosis, as a sequela, 182. 
Anaemia, 82. 

post malarial, 85, 182. 

pernicious, as a sequela, 183, 197. 

prognosis of, 197. 
Anopheles claviger, 35, 68. 

pictus, 35. 

nigripes, 35. 
Anopheles, methods of distinguishing, 

35, 39. 
Aphasia, as a sequela, 178. 
Arteritis, as a sequela, 179. 

Bacteria in malaria, 5. 

Blood, examination of, 16, 22, 48, 166, 185. 

examination of during clinical pe- 
riods, 19, 21, 119. 

methods of staining of, 50. 

objects mistaken for parasites in, 49. 

general pathology of, 79. 
Bone marrow, changes in, 98. 
Brain, 92. 

blood-vessels of, 92. 

changes in nerve cells of, 93. 

endothelial cells in, 93. 

free parasites in, 93. 

free pigment in, 93. 

macrophages in, 93. 

pathology of, 92. 

pigmented leucocytes in, 93. 

segmentation in, 92. 
Bronchitis, acute, complicating, 109. 

Cachexia, 88, 183, 198. 

prognosis of, 184, 198. 

as a sequela, 183^ 

treatment of, 213. 
Camp, choice of, 203. 



Cadaver, appearance of, 92. 
Cardiac weakness, treatment of, 212. 
Cardialgic form, prognosis of, 154. 
Cells, endothelial, phagocytic action of, 
43. 

splenic pulp, 43. 

bone marrow, 43. 
Chills in estivo-autumnal malaria, 110. 
Cholera, differential diagnosis from, 194. 
Choleraic form, 153. 

prognosis of, 196. 
Chromatin, staining reactions of, 54. 
Climate, influence of, 59. 
Classification, 45. 

morphological, 45. 

clinical, 104. 
Collapse, treatment of, 212. 
Complications, 168. 

circulatory system, 170. 

digestive system, 171. 

genito-urinary system, 170. 

excretory system, 170. 

nervous system, 168. 

respiratory system, 168. 
Convalescence, change of climate during, 
213. 

diet during, 213. 

treatment during, 213. 
Corpuscles, red blood, 8, 9. 

color of, 8, 9. 

shape of, 8, 9. 

destruction of, 79, 82. 

hemoglobin in, 79, 84. 

number of parasites in, 8. 

parasites in, 8, 9. 

reduction of, 82. 
Corpuscles, white, reduction of , 84. 
Countries, malarial, 58. 
Crescents, degeneration of, 10. 

development of flagellated form from, 
29. 

development of, in mosquito, 37. 

discovery of, 6. 

distinction between tertian and quo- 
tidian, 25. 

fertilization of, 31 . 



(215) 



216 



INDEX 



Crescents, fragmentation of, 26. 

in the bone marrow, 98. 

in the spleen, 97- 

nature of, 32. 

origin of, 32. 

outline of, 9, 24. 

pigment in, 9, 24. 

protoplasm of, 24. 

quotidian, 25. 

significance of, 32. 

staining reactions of, 55. 

tertian, 25. 

time of occurrence of, 24. 

vacuolization of, 25. 
Cultivation experiments, 40. 
Cycle of the estivo-autumnal parasites, 11. 

Daytime as predisposing cause, 59. 
Deafness, as a sequela, 182. 
Diaphoretic form, symptoms of, 155. 

prognosis of, 196. 
Diagnosis, of the quotidian form, 186. 
of the tertian form, 186. 
of pernicious forms, 186. 
of irregular and continued forms, 187. 
by examination of the blood, 51, 185. 
Diagnosis, differential, from typhoid, 188. 

from tuberculosis, 191. 

from hepatic abscess, 191. 

from ulcerative endocarditis, 191. 

from yellow fever, 191. 

from cholera, 194. 

from dysentery, 194. 

from uraemia, 194. 

from leukaemia, 194. 

from purpura haemorrhagica, 194. 

from hemiplegia, 194. 

from multiple neuritis, 194. 
Diet during treatment, 204. 
Digestive system, diseases of as sequela, 
179. 

diseases of, as complications, 171. 
Distribution of estivo-autumnal fevers, 

58. 
Drapanidium, 45. 
Dysenteric forms, prognosis of, 196. 

symptoms of, 155. 
Dysentery, as a complication, 171. 

Endocarditis, as a sequela, 179. 

as a complication, 170. 

ulcerative, differential diagnosis from, 
191. 
Enteritis, as a complication, 171. 

ulcerative, as a sequela, 179. 



Erysipelas, as a complication, 175." 
Etiology, 58. 
Euchinin, 211. 

Facial appearance, 107, 115. 
Fever, definition of estivo-autumnal, i. 
cause of variations in, 12, 111. 
continuous, 161. 
crisis of, 107. 
effect of quinine on, 121. 
etiology of, 88. 
incubation of, 71. 
latent or masked, 159. 
modifications of, 11, 111, 162. 
pseudocrisis of, 108. 
quotidian estivo-autumnal, 11, 108, 

112, 121. 
remittent, 161. 
subcontinued, 161. 
temperature curve of, 11, 108, 112. 
tertian estivo-autumnal, 12, 106, 132. 
variations in, 12, 111. 
Flagella, size of, 28. 
action of, 28. 
pigment in, 28. 
fragmentation of, 29. 
Flagellate bodies, 6, 10, 26. 
activity of, 28. 
active form of, 27. 
pigment in, 27. 
degeneration of, 15, 29. 
development of active form of, 

27, 29. 
varieties of, 26. 
methods of obtaining, 26. 
origin of, 26, 33. 
passive form of, 30. 
pigment in passive form of, 

30. 
significance of, 31-33. 
sexual nature of, 31, 33. 
staining reactions of, 56. 
Fusiform bodies, 26. 

Gametes, 37. 
Micro, 37. 
Macro, 37. 
Gametocytes, Micro, 37. 
Gastritis as a complication, 171. 
Gastro-intestinal tract, diseases of, com- 
plicating, 171. 
diseases of, as sequelae, 179. 
Genito - urinary system, diseases of, as 
complications, 170. 
diseases of, as sequelae, 179. 



INDEX 



217 



Glycosuria as a sequela, 181. 
(Jymnosporidia, 45. 

Haaniamoeba nialariae, 6. 
immaculata, 45. 
precox, 45. 
selicta, 45. 
sub-immaculata, 45. 
sub-prascox, 45. 
vivax, 45. 
Hsemoproteus, 45. 
Heemosporidia, 45. 
Haamorrhagic form, prognosis of, 

196. 
Hemosiderin, 81. 

chemical nature of, 82. 
distribution of, 82. 
Halteridium, 45. 
Headache, treatment of, 212. 
Heart, pathology of, 95. 
Hemiplegia as a complication, 151. 

differential diagnosis from, 191. 
Hemoglobin, retraction of, 49, 79. 

reduction of, 84. 
Hepatic abscess, differential diagnosis 

from, 191. 
Hepatitis as a sequela, 181. 
Historical, 4. 

Hyaline bodies, discovery of, 6. 
quotidian, 17, 123. 
size of quotidian, 17, 123. 
shape of quotidian, 17, 123. 
activity of quotidian, 17, 123. 
number in the infected corpuscle 

of, 18, 123. 
tertian, 20, 136. 
size of tertian, 20, 136. 
shape of tertian, 20, 136. 
staining reactions of, 53. 
activity of tertian, 20, 136. 
number in the infected corpus- 
cle of, 20, 136. 
Hysteria as a complication, 151. 

Immunity, 74. 

acquired, 75. 

congenital, 75. 

racial, 75. 
Incubation, period of, 71. 
Infection, combined, 16. 

by air, 62. 

by water, 62. 

by inoculation, 63. 
Inflammation, phlegmonous, as a com- 
plication, 175. 



Inoculation, direct infection by, 41, 63. 

experiments in, 41, 63. 

the mosquito and inoculation, 63. 

transmission from man to man by, 
41. 
Insanity, as a sequela, 178. 
Insolation, as a complication, 175. 
Iritis, as a complication, 182. 

Keratitis, as a sequela, 182. 
Kerosene, as a prophylactic, 200. 
Kidneys, pathology of, 97. 

Latent or masked fever, 159. 
Laverania malaria, 45. 

ranarum, 45. 

Danilewski, 45. 
Lemons, as a substitute for quinine, 212. 
Leucocytes, 84, 93. 

decrease of, 84. 

increase of, 84. 

pigment in, 42. 
Leucocytosis, 84. 

apparent, 84. 

real, 84. 
Leuk33mia,differential diagnosis from, 194. 
Liver, pathology of, 95. 

cirrhosis of, 181. 
Locality, as a predisposing cause, 58. 
Locality in prognosis, 196. 
Lungs, pathology of, 94. 

Macrophages, 43, 93. 

Malaria, Classification of, 3, 104. 

pernicious forms of, 147. 

quartan, 7. 

quotidian, estivo- autumnal, 15, 22, 
108, 121. 

tertian, 7. 

tertian estivo-autumnal, 15, 22, 106, 
108, 132. 
Mania as a complication, 168. 
Mania as a sequela, 178. 
Masked or latent fever, 159. 

medicinal treatment of, 205. 
Melancholia as a sequela, 178. 
Melanaamia, 80. 
Melanin, chemical nature of, 81. 

distribution of, 81. 
Meningitis as a complication of, 168. 
Mental sequela, prognosis of, 197. 
Methylene blue as a substitute for qui- 
nine, 211. 
Mosquito theory, 18, 19, 35, 63. 
evidence in favor of, 63. 



218 



INDEX 



Mosquito experimental evidence of, infec- 
tion by, 65. 
historical, 36. 
Mosquitoes, conditions affording protec- 
tion from, 199, 203. 
development of parasites within, 37, 

68. 
differentiation of, 39. 
methods of study of, 35. 
situation of parasite within, 37, 68. 
types of, 35. 
Moisture as a predisposing cause, 60. 

Nausea, 112, 212. 

Nephritis, as a complication, 170. 

as a sequela, 180. 

prognosis of, 197. 
Nervous system, diseases of, as complica- 
tions, 151. 

diseases of, as sequela?, 178. 

symptoms connected with, 118. 
Neuralgia, as a sequela, 178. 
Neuritis, multiple, as a sequela, 178. 

differential diagnosis from, 194. 

Occupation as a predisposing cause, 61. 
Occupation in prognosis, 197. 
Optic neuritis, as a sequela, 182. 
Orchitis, as a complication, 170. 
Oscillaria malaria?, 45. 
Otalgia, as a sequela, 182. 
Ovoid bodies, in brain, 93. 

in spleen, 96. 

development of, 26. 

discovery of, 6. 

origin of, 26, 32. 

quotidian, 26. 

significance of, 32. 

staining reactions of, 55. 

tertian, 26. 

time of occurrence of, 24. 

Paralysis as a sequela, 178. 
Paraplegia as a complication, 168. 
Parasites, in estivo-autumnal fever, 6, 7, 
17, 123, 136. 

action of quinine on, 205. 

amoeboid movements of, 18, 123, 136. 

classification of, 11, 17, 45. 

crescent forms of, 7, 24, 55. 

cultivation of, 40. 

description of, 6, 7, 17, 123, 136. 

development of in mosquito, 35, 68. 

diagnostic value of, 4. 

discovery of, 6. 



Parasites, flagellated forms of, 6, 26, 56. 
ring forms of, 7, 17, 20, 53, 123, 136. 
intracorpuscular, 7, 17, 123, 136. 
inoculation of, 41. 
methods of staining of, 50. 
ovoid forms of, 6, 24, 26, 55. 
varieties of, 6, 7. 
pigmented forms of, 8, 18, 21, 54. 
protoplasm in, 17, 20, 123, 136. 
segmenting forms of, 8, 18, 21, 123, 

136. 
study of, in blood, 19, 22, 48. 
Quotidian estivo-autumnal parasite, 11, 
123. 

amoeboid movement of, 17, 123. 

crescentic form of, 25, 123. 

cultivation of, 40. 

effect of quinine on, 205. 

flagellate forms of, 26. 

hyaline form of, 17, 123. 

life cycle of, 16, 31, 34, 38. 

ovoid forms of, 24. 

pigmented forms of, 16, 123. 

relation to paroxysm, 19, 119. 

shape of, 17, 123. 

size of, 17, 123. 

segmentation of, 18, 123. 

structure of, 17, 123. 
Tertian estivo-autumnal parasite, 20, 
136, 146. 

amoeboid movement of, 20, 136. 

crescentic forms of, 25, 136. 

effect of quinine on, 205. 

flagellate forms of, 26. 

hyaline form of, 20, 136. 

life cycle of, 16, 31, 34, 38. 

ovoid forms of, 24. 

pigmented forms of, 21, 136. 

relation to paroxysm, 21, 119. 

shape of, 20, 136. 

size of, 20, 136. 

segmenting forms of, 21, 136. 

differential diagnosis, 23, 45. 
Paraplegia as a complication, 168. 
Parotitis as a complication, 175. 
Pathology, general, 79. 

special, 91. 
Pernicious estivo-autumnal malaria, 147. 

the algid form, 152. 

the ataxic form, 152. 

the bilious form, 156. 

bulbar paralysis in, 152 

cause of, 149. 

classification of, 148. 

comatose form, 149. 



INDEX 



219 



Pernicious estivo-autumnal malaria— 
cardialgic form, 154. 
choleraic form, 153. 
differential diagnosis of, 192. 
examination of blood in, 157 
the delirious form, 151. 
the diaphoretic form, 155. 
the dysenteric form, 155. 
the eclamptic form, 151. 
examination of the blood in, 142. 
the gastralgic form, 154. 
the haemorrhagic form, 155. 
parasites in, 147. 
the pneumonic form, 155. 
the syncopal form, 156. 
treatment of, 208. 
Phagocytes, 42. 

degeneration of, 43. 
substances taken up by, 44. 
varieties of, 43. 
Phagocytosis, action of quinine upon, 44. 
significance of, 44. 
time of occurrence of, 43. 
Phenocoll, 212. 
Pigment, yellow, 81. 
distribution of, 82. 
black, 81. 
Pigmented bodies, quotidian, 18, 123. 
tertian, 21, 136. 
staining reactions of, 54. 
Pleurisy, as a complication, 170. 
Polyuria, as a sequela of, 181. 
Pneumonia, as a complication, 169. 
Prognosis, 194. 

in algid form, 195. 

in cardialgic form, 196. 

in choleraic form, 196. 

in diaphoretic form, 196. 

in dysenteric form, 196. 

in haemorrhagic form, 196. 

in comatose form, 195. 

effect of age upon, 196. 

effect of location upon, 196. 

effect of occupation upon, 197. 

effect of race upon, 196. 

effect of physical condition upon, 197. 

factors influencing, 196. 

in complications, 197. 

in malarial cachexia, 198. 

of nephritis, 197. 

of nervous sequelae, 197. 

of sequelae, 197. 

of pernicious forms, 195. 

of pernicious cerebral forms, 195. 

of post malarial anemia, 196. 



Prognosis — 

of pneumonic form, 196. 

of quotidian type, 194. 

of tertian type, 195. 
Predisposition, altitude in, 59. 

age in, 61. 

climate in, 59. 

locality in, 58. 

moisture in, 60. 

occupation in, 61 

race in, 61. 

rain in, 60. 

sex in, 61. 

soil in, 60. 

time of day in, 59. 

winds in, 60. 
Prophylaxis, choice of camp in, 203. 

drinking water in, 203. 

general, 199. 

personal, 203. 

use of kerosene in, 200. 

use of mosquito nets and screens in, 
203. 

destruction of mosquitoes in, 199. 

use of odorous principles in, 204. 

use of quinine in, 204. 
Proteosoma, 45. 

Quartan malaria, parasite of, 7. 
Quinine as a prophylactic, 204. 
as a test for malaria, 4. 
contra-indications to use of, 211. 
effect upon parasites of, 205. 
form of, to be administered, 207. 
method of administration of, 208. 
influence on temperature curve of, 

12, 15, 16, 121. 
salts of, 207. 

time of administration of, 206. 
substitutes for, 211. 
Quotidian estivo-autumnal fever, 108,121. 

afebrile stage of, 112. 

bone marrow in, 98. 

brain in, 92. 

clinical description of, 108, 121. 

chill in, 112. 

distribution of, 58, 104. 

heart in, 95, 116. 

kidneys in, 97, 118. 

liver in, 95, 118. 

lungs in, 94, 116. 

mouth and tongue in, 115. 

paroxysms in, 108. 

phagocytosis in, 44. 

prodromal symptoms of, 108. 



220 



INDEX 



Quotidian estivo-autumnal fever 
prognosis of, 194. 
remittent fever of, 112. 
retina in, 94. 
skin in, 115. 
spleen in, 96, 116. 
symptomatology of, 108. 
stomach and intestines in, 95, 116. 
temperature curve of, 108. 
time of occurrence of, 104. 
urine in, 86, 118. 

Race as a predisposing cause, 61. 
Race in prognosis, 196. 
Rain as a predisposing cause, 60. 
Recovery, spontaneous, 76. 

cause of, 76. 
Remittent estivo-autumnal fever, 161. 
Respiratory system, symptoms connected 
with, 116. 
complications connected with, 151. 
Retina, changes in, 94. 
Retinitis as a sequela, 182. 
Rheumatism as a complication, 175. 
Rhizopoda, 45. 

Sciatica, as a complication, 175. 
Season, the malarial, 64, 104. 
Segments, size of, 18, 21, 123, 136. 

staining reactions of, 54. 
Segmentation, 18, 21. 

activity of pigment in, 18, 21. 

appearance of pigment in, 18, 21. 

description of parasites in, 18, 21. 

frequency of, in blood, 18, 21. 

in spleen, 18, 21. 

of quotidian parasite, 18. 

of tertian parasites, 21. 

occurrence of, in corpuscles, 18, 21, 
123, 136. 

relation of, to paroxysm, 7. 
Sequelae, 175. 

nervous system, 178. 

circulatory system, 179. 

digestive system, 179. 

genito -urinary system, 179. 

glandular system, 181. 

organs of sense, 182. 

treatment of, 213. 
Sex, as a predisposing cause, 61. 
Soil, as a predisposing cause, 60. 
Spleen, changes in, 96. 

abscess of, as a sequela, 182. 

crescent forms in, 8, 97. 

enlargement of, 96, 181. 



Spleen, floating, 181. 

pathology of, 96. 

puncture of, 16. 

rupture of, 181. 
Spores in etiology of malaria, 5. 
Sporozoa, 6, 45. 
Sporozoites, 38. 
Staining, 51. 

methods of, 50. 

Chenzinsky s method of, 51. 

Futcher's method of, 52. 

Laveran's method of, 52. 

•Nocht-Romanowsky's method of, 57. 

Romanowsky's method of, 50. 
Stomach, pathology of, 95. 
Sweating, 115. 
Symptomatology, 108. 

Temperature curve of, in tertian form, 
11, 15, 108. 
curve of, in quotidian form, 11, 15, 

112. 
analysis of, 11, 15, 108, 112. 
irregular, 12, 15, 109. 
parasites, in relation to, 22. 
remittent form of, 114, 161. 
Tertian estivo-autumnal fever, 106, 132. 

afebrile stage of, 108. 

brain in, 92, 118. 

bone marrow in, 98. 

clinical description of, 108, 132. 

distribution of, 164. 

febrile stage of, 108. 

frequency of, 105. 

heart in, 95, 116. 

kidneys in, 97, 118. 

liver in, 95, 118. 

lungs in, 94, 116. " 

mouth and tongue in, 115. 

paroxysm of, 107. 

prodromal symptoms of, 107. 

prognosis of, 195. 

remittent fever of, 111. 

stage of remission of, 108. 

stomach and intestines in, 95, 116. 

skin in, 115. 

sweating in, 115. 

symptomatology of, 107. 

temperature curve of, 11, 15, 108. 

time of occurrence of, 104. 

urine in, 86, 118. 
Tonsilitis, as a complication, 175. 
Treatment, 204. 

change of climate during, 205. 
diet during, 204. 



INDEX 



221 



Treatment— 

of convalescence, 213. 

hygienic, 204. 

medicinal, 205. 

of algid symptoms, 212. 

of cardiac weakness, 212. 

of collapse, 212. 

of complications, 213. 

of headache, 212. 

of high temperature, 212. 

of pernicious attacks, 208. 

of sequelse, 213. 

of vomiting, 213. 

quinine in, 205. 

of special symptoms and complica- 
tions, 212. 
Tropics, in relation to malaria, 3, 59, 

104. 
Tuberculosis, as a complication, 169. 

differential diagnosis of, 191. 
Typhoid, as a complication, 171. 

differential diagnosis from, 188. 

combined infection with, 171. 

Urinary system, symptoms connected 
with, 118. 



Urine, 86. 

acidity of, 87. 

albumin in, 88. 

amount of, 86. 

chlorides in, 87. * 

color of, 87. 

indican in, 88. 

iron in, 88. 

sodium and potassium in, 88. 

specific gravity of, 87. 

solids in, 87. 

urea in, 87. 

uric acid in, 87. 

Vacuoles, 49. 

Variola, as a complication, 175. 

Vertigo, as a sequela, 182. 

Vegetable cells in, 5. 

Viscera, pathological changes in, 91. 

Vomiting, 116. 

treatment of, 212. 

Water, direct infection by, 62. 

boiling of, 203. 
Winds as a predisposing cause, 60. 

Yellow fever, differentia] diagnosis of, 191. 



